|
 |
| ORIGINAL ARTICLE |
|
| Year : 2015 | Volume
: 11
| Issue : 42 | Page : 404-409 |
|
|
Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway
Xiang-An Zhang1, Shuangxi Zhang1, Qing Yin2, Jing Zhang1
1 Anorectal Disease Center, The First Affiliated Hospital, Henan College of TCM, Zhengzhou 450000, China
2 Department of Hematological Malignancy, The Affiliated Hospital, Henan TCM Research Academy, Zhengzhou 450000, China
| Date of Submission | 13-May-2014 |
| Date of Acceptance | 12-Jun-2014 |
| Date of Web Publication | 12-Mar-2015 |
Correspondence Address:
Xiang-An Zhang
Anorectal Disease Center, The First Affiliated Hospital, Henan College of TCM, No. 19, Renmin Road, Zhengzhou 450000
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0973-1296.153096
 Abstract | | |
Quercetin can inhibit the growth of cancer cells with the ability to act as chemopreventers. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-kB) is a signaling pathway that controls transcriptional activation of genes important for tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-kB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In this study, we demonstrate that quercetin induces apoptosis in human colon cancer CACO-2 and SW-620 cells through inhibiting NF-kB pathway, as well as down-regulation of B-cell lymphoma 2 and up-regulation of Bax, thus providing basis for clinical application of quercetin in colon cancer cases. Keywords: Apoptosis, colon cancer, nuclear factor-kappa B, quercetin
How to cite this article:
Zhang XA, Zhang S, Yin Q, Zhang J. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway. Phcog Mag 2015;11:404-9 |
How to cite this URL:
Zhang XA, Zhang S, Yin Q, Zhang J. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway. Phcog Mag [serial online] 2015 [cited 2022 Jun 27];11:404-9. Available from: http://www.phcog.com/text.asp?2015/11/42/404/153096 |
| Introduction | |  |
Colon cancer is one of the most prevalent cancers throughout the world and especially in the Western countries. Many epidemiological studies indicated that western style diet such as consumption of red meats is possibly associated with a high colon cancer incidence. [1] Despite earlier detection and dropping death rates in colon cancer, 112,340 new cases were estimated for 2007. [2] The most common treatment for colon and rectal cancer is surgical resection, followed by adjuvant therapy with 5-fluorouracil, oxaliplatin, and leucovorin. Early detection can provide a 5-year survival rate of up to 90%, and surgery is most often curative. However, if patients present with distant metastasis at the time of diagnosis, the 5-year survival rate drops to only 10%. [2] Despite recent improvements in surgical techniques and chemotherapy, advanced colon cancer continues to have poor clinical outcomes. Molecules intimately related to cancer cell survival, proliferation, invasion, and metastasis have been studied as candidates for molecular targeted agents. [3]
Dietary polyphenolic compounds have showed various pharmacological activities including anti-cancer activity. [4],[5],[6],[7],[8],[9],[10] Quercetin (3,3',4', 5, 7-pentahydroxyflavone) [Figure 1]a, an important dietary polyphenol present in red onions, apples, berries, citrus fruits, tea, and red wine, [11] exhibits anti-oxidant, anti-inflammatory, anti-obesity and anti-cancer properties. [12] Quercetin has received increasing attention as a pro-apoptotic flavonoid with specific and almost exclusive activity on tumor cells rather than normal, nontransformed cells. [13],[14] However, the mechanisms by which quercetin exerts its anti-cancer activity remain unclear. | Figure 1: Inhibitory effect of quercetin on cell viability of human colon cancer cells. (a) Chemical structure of quercetin; (b) human colon cancer CACO-2 and SW-620 cells were treated with quercetin with designated concentrations, and cells viability were detected using Cell Counting Kit-8 assay at 6 h (diamond) and 24 h (triangle)
Click here to view |
The nuclear factor-kappa B (NF-kB) pathway is thought to play an important role in the process leading from inflammation to carcinogenesis and thus may be a candidate for targeted intervention. [15],[16],[17] Multiple pro-inflammatory stimuli activate NF-kB, primarily through inhibitor of kB kinase (IKK)-dependent phosphorylation and ubiquitin-mediated degradation of IkB proteins. Once activated, NF-kB stimulates the transcription of genes encoding cytokines, growth factors, chemokines, and anti-apoptotic factors. [18],[19] Moreover, NF-kB pathway has also been implicated in tumor initiation, progression, metastasis, and resistance to chemotherapy. [17],[20] In colon cancer, NF-kB is constitutively activated. [21],[22] Aberrant NF-kB activation results in enhanced proliferation, [23] evasion of apoptosis, [23],[24],[25] genomic instability, [26] increased rate of glycolysis [27] and drug resistance [28] in colon cancer cells.
Studies have suggested a series of pharmacologic inhibitors of NF-kB pathway to be potential anti-cancer agents, [20],[29] such as IkB or IKK inhibitors, [30] ammonium pyrrolidinedithiocarbamate, [31] as well as selective ubiquitin proteosome inhibitors. [32] However, there still has no comprehensive investigation for anti-tumor effect of NF-kB inhibitors on colon cancer.
Our present study demonstrated that quercetin presented potent anticancer effects within an inhibitory effect on NF-kB, and could induce apoptosis of colon cancer cells in vitro, thus providing basis for clinical application of quercetin in colon cancer cases.
| Materials and methods | | |
Reagents and antibodies
Quercetin, glyceraldehyde 3-phosphate dehydrogenase was purchased from Sigma Chemical Co (St. Louis, MO, USA). Antibodies including phosphorylated and nonphosphorylated forms of IkB-α and NF-kB were purchased from Cell Signaling Technology Inc. (Beverly, MA, USA). Dulbecco's modified Eagle's medium (DMEM) and fetal bovine serum were purchased from GIBCO BRL.
Cell culture
Human colon cancer CACO-2 and SW-620 cells were obtained from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China). Cells were incubated in DMEM (high glucose), 10% fetal bovine calf serum, 100 U/ml penicillin-streptomycin. Cells were maintained at 37°C in a humidified atmosphere of 95% air and 5% CO 2 .
Cell viability assay
Cell viability was quantified by Cell Counting Kit-8 (CCK-8) (Beyotime, China) assay according to the manufacturer's instructions. In brief, CACO-2 and SW-620 cells were seeded into 96-well plates at a density of 2 × 10 3 cells/well. After incubation overnight, cells were treated as indicated concentration of quercetin and assessed by CCK-8 assay at 6 and 24 h respectively. 10 μl of CCK-8 reagent was added to each well and incubated for 1 h. The difference in absorbance between 450 and 630 nm was measured by a microplate reader (BioTek, Winooski, VT, USA) as an indicator of cell viability. Independent experiments were done in triplicate. About 50% growth inhibitory concentration (IC 50 ) values were calculated as the concentration of the compound that inhibited the viability of cells by 50% as compared with control cells grown in the absence of inhibitor.
Cell lysis and immunoblotting
Cells were lysed, and proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to polyvinylidene difluoride membrane (Immobilon; Millipore, Billerica, MA). Immunoblotting was done with different antibodies and visualized by an enhanced chemiluminescence (Amersham, Piscataway, NJ) method.
Nuclear factor kappa-B transcription factor assay
Nuclear factor kappa-B (NF-kB) p65 subunit DNA binding activity was determined by an enzyme-linked immunosorbent assay (Cayman Chemicals, Ann Arbor, MN, USA) according to the manufacturer's instructions. In brief, a specific double stranded DNA sequence containing the NF-kB (p65) response element was immobilized onto the bottom of wells of a 96-well plate. Nuclear extracts were added to the plate and incubated overnight at 4°C without agitation NF-kB (p65) was detected by addition of a specific primary antibody directed against p65. A secondary antibody conjugated to horseradish peroxidase was added to provide a sensitive colorimetric readout at 450 nm. Independent experiments were done in triplicate. Nuclear extract from cells was prepared using Nuclear Extraction Kit (Millipore, Watford, UK) according to manufacturer's instructions.
Hoechst-33258 staining
CACO-2 and SW-620 cells were seeded in 12-well culture dishes (5 × 10 4 cells/well). After experimental treatment, cells were washed twice with phosphate buffered solution (PBS), and stained with Hoechst-33258 (5 mg/ml) for 5 min in the dark, and then followed by extensive washes. Nuclear staining was examined under a fluorescence microscope, and images were captured using ImagePro Plus software (Media Cybernetics, Silver spring, MD).
Cell apoptosis assay
Cell apoptosis detection was performed using an Annexin-V-FITC Apoptosis Detection Kit (BD company, US) according to the manufacturer's protocol. Briefly, cells were collected after 24 h treatment with quercetin. The cells were washed twice with cold PBS then resuspended in 1 × binding buffer at a concentration of 1 × 10 6 cells/ml. Then 500 μl cell suspension was incubated with 5 μl Annexin-V-FITC and 10 μl PI for 15 min in the dark and analyzed by a FACScalibur instrument (Becton Dickinson, San Jose, US) within 1 h. Apoptotic cells were those stained with Annexin V + /PI− (early apoptosis) plus Annexin V+/PI+ (late apoptosis).
Statistical analysis
Results were presented as mean ± standard deviation differences between two groups were tested using Student's t-test; two-way analysis of variance analysis was performed where indicated. Statistical significance was determined at the level of P < 0.05.
| Results | | |
Inhibitory effects of quercetin on viability of human colon cancer cells in vitro
To identify whether quercetin influence the survival of CACO-2 and SW-620 cells, cells were treated with 0-200 μM quercetin, and after that cell viability was examined by CCK-8 assay. As shown in [Figure 1]b, both CACO-2 and SW-620 cells viability are dramatically suppressed after treating with 200 μM quercetin, when compared to the negative control (0 μM). After 24 h, quercetin showed high inhibition of cell population growth in a dose-dependent manner with IC 50 values of 35 μM (CACO-2 cells) and 20 μM (SW-620 cells).
Inhibitory effect of quercetin on nuclear factor kappa-B activity in colon cancer cells
We further detected the inhibitory effect of quercetin on NF-kB activity in CACO-2 and SW-620 cells. As shown in [Figure 2], NF-kB DNA binding activity was dramatically decreased after quercetin treatment for 6 h. Moreover, quercetin also induced the dephosphorylation and up-regulation of IkB-α [Figure 3]. Taken together, these results suggested that quercetin displayed rapid and potent anti-tumor effects against colon cancer cell lines. | Figure 2: Nuclear factor kappa-B DNA binding activity after quercetin treatment for 6 h was determined using an enzyme-linked immunosorbent assay. Data were expressed as means ± standard deviation (n = 3). The experiments were repeated twice. *P < 0.05 significantly different from control (0 μM); **P < 0.01 significantly different from control (0 μM); ***P < 0.001 significantly different from control (0 μM)
Click here to view |
 | Figure 3: The inhibitory effect of quercetin on IêBa phosphorylation and nucleus translocation of Nuclear factor kappa-B p65 subunit in CACO-2 and SW-620 cells was detected using western blot at 6 h. Glyceraldehyde 3-phosphate dehydrogenase as controls for loading of total cell lysates and nuclear extracts respectively
Click here to view |
Quercetin induced CACO-2 and SW-620 cells apoptosis
The apoptotic effect of quercetin was analyzed and quantified by flow cytometry using the Annexin V-FITC Apoptosis Detection Kit. As shown in [Figure 4], quercetin induced CACO-2 and SW-620 cells apoptosis in a dose-dependent manner. | Figure 4: Quercetin induces apoptosis in a dose-dependent manner. The apoptotic fraction of CACO-2 and SW-620 cells was detected by Annexin V-PE and PI double staining
Click here to view |
Apoptotic events of Hoechst-33258 staining were also tested. After exposed to three concentrations of quercetin (0 μM, 25 μM and 50 μM) for 24 h, apoptosis of CACO-2 and SW-620 cells was demonstrated by Hoechst-33258 staining, revealed cell membrane permeability increasement and nuclear condensation [Figure 5]. | Figure 5: Hoechst 33258 staining analyzed the cell apoptosis after indicated treatments using a fluorescence microscope, ×100
Click here to view |
In order to gain a better insight into pro-apoptotic effect of quercetin, we detected protein expression of apoptosis marker molecular. Poly (ADP-ribose) polymerase (PARP) was one of the main cleavage targets of caspase-3 and cleaved PARP always served as a marker of cells undergoing apoptosis. [33] Results demonstrated that cleaved PARP could not be detected until quercetin treated was administrated at the high dose of 30 μM, further suggesting that quercetin could induce apoptosis in a dose-dependent manner [Figure 6]. We also measured the expression of apoptosis inducing factor (AIF), which played a critical role in caspase-independent apoptosis. [34] However, results demonstrated that no increase in AIF expression was detected after quercetin treatment [Figure 6]. | Figure 6: Protein expression of cleaved poly (ADP-ribose) polymerase and apoptosis inducing factor in CACO-2 and SW-620 cells after indicated treatments was measured by western blots. Glyceraldehyde 3-phosphate dehydrogenase served as a control for loading
Click here to view |
B-cell lymphoma 2 family proteins were involved with quercetin induced apoptosis
We next investigated the expression of B-cell lymphoma 2 (Bcl-2) families, which regulated mitochondrial apoptosis and could be separated into pro-survival members (such as Bcl-2, Bcl-extra large (Bcl-xL), and myeloid cell leukemia-1), as well as pro-apoptotic proteins (such as Bax). [35],[36] As shown in [Figure 7], after quercetin treatment, Bcl-2 is down-regulated significantly, and Bax is up-regulated on the contrary. These results are consisted with the general notion that Bcl-2 and Bax play a pivotal role in regulating mitochondrial apoptosis pathway. [37] | Figure 7: Mitochondrial pathway is involved in the apoptotic effects of quercetin. Protein expression of cleaved caspase 3, 9, as well as B-cell lymphoma 2, Bax in CACO-2 and SW-620 cells after indicated treatments was measured by western blots
Click here to view |
| Discussion | | |
Dietary phytochemicals consist of a wide variety of biologically active compounds that are ubiquitous in plants, many of which have been reported to have anti-tumor properties. Epidemiological studies have shown that the consumption of vegetable, fruits, and tea is associated with a decreased risk of cancer and cardiovascular diseases, and polyphenols are believed to play an important role in preventing these diseases. [38],[39] Among them, quercetin has been reported to have therapeutic potential for treating many human cancers. [11],[12],[13],[14]
An enormous amount of data strongly implicate that the inhibition of NF-kB signaling could be potentially effective in suppressing inflammation or tumor progression, and development of new small molecule inhibitors of this pathway is needed. [40],[41] Recently, studies have been made in the design of potent orally active NF-kB pathway inhibitors for anti-inflammation or anti-tumor purposes. [42],[43],[44],[45] Compounds that inhibited the NF-kB pathway could lead to the decreased expression of endothelial cell adhesion molecules. [46] Further studies searching for alternative therapeutic strategies against malignancies have shown that it is a potent inducer of apoptosis in a number of malignant cells such as in colorectal cancer, [47] breast cancer, [48] and hematological malignants. [49],[50],[51] In this study, we showed the potent anti-tumor effects of quercetin as a novel NF-kB inhibitor against human colon cancer in vitro.
In colon cancer cells, NF-kB is always constitutively activated, [21],[22] and contributes to enhanced proliferation [23] and evasion of apoptosis. [23],[24],[25] Degradation of IkB release NF-kB proteins to the nucleus where they transactivate approximately 300 target genes, including those encoding regulators of pro-survival factors, such as Bcl-2, [52] Bcl-xL. [40] NF-kB is an important inhibitor of apoptosis and can protect cancer cells from cell death induced by tumor necrosis factors (TNFα) or TNF superfamily members, different pharmaceuticals or irradiation. [53] In this study, we found that quercetin could down-regulate Bcl-2 as well as up-regulate Bax, which may contribute to this apoptosis induction. However, the exact mechanism how quercetin induces mitochondrial dysfunction and cellular apoptosis also needs further investigation.
| Conclusions | | |
Quercetin could induce human colon cancer cells apoptosis via inhibiting NF-kB pathway. Since quercetin showed potent inhibition on the proliferation of human colon cancer cells, it had the potential to be developed into a drug candidate for treating human colon cancers.
| References | | |
| 1. | Boateng J, Verghese M, Shackelford L, Walker LT, Khatiwada J, Ogutu S, et al. Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Food Chem Toxicol 2007;45:725-32.  |
| 2. | Fuller-Pace FV. The DEAD box proteins DDX5 (p68) and DDX17 (p72): Multi-tasking transcriptional regulators. Biochim Biophys Acta 2013;1829:756-63. |
| 3. | Patil JR, Jayaprakasha GK, Chidambara Murthy KN, Tichy SE, Chetti MB, et al. Apoptosis-mediated proliferation inhibition of human colon cancer cells by volatile principles of Citrus aurantifolia. Food Chem 2009;114:1351-8. |
| 4. | Fan H, Wu D, Tian W, Ma X. Inhibitory effects of tannic acid on fatty acid synthase and 3T3-L1 preadipocyte. Biochim Biophys Acta 2013;1831:1260-6. |
| 5. | Wu D, Ma X, Tian W. Pomegranate husk extract, punicalagin and ellagic acid inhibit fatty acid synthase and adipogenesis of 3T3-L1 adipocyte. J Funct Food 2013;5:633-41. |
| 6. | Wang Y, Tian WX, Ma XF. Inhibitory effects of onion ( Allium cepa L.) extract on proliferation of cancer cells and adipocytes via inhibiting fatty acid synthase. Asian Pac J Cancer Prev 2012;13:5573-9. |
| 7. | Quan X, Wang Y, Ma X, Liang Y, Tian W, Ma Q, et al. A-Mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells via inhibiting fatty acid synthase. PLoS One 2012;7:e33376. |
| 8. | Jiang HZ, Quan XF, Tian WX, Hu JM, Wang PC, Huang SZ, et al. Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostana. Bioorg Med Chem Lett 2010;20:6045-7. |
| 9. | Li P, Tian W, Wang X, Ma X. Inhibitory effect of desoxyrhaponticin and rhaponticin, two natural stilbene glycosides from the Tibetan nutritional food Rheum tanguticum Maxim. ex Balf. on fatty acid synthase and human breast cancer cells. Food Funct 2014;5:251-6. |
| 10. | Jiang HZ, Ma QY, Fan HJ, Liang WJ, Huang SZ, Dai HF, et al. Fatty acid synthase inhibitors isolated from Punica granatum L. J Braz Chem Soc 2012;23:889-93. |
| 11. | Erlund I. Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 2004;24:851-74. |
| 12. | Gibellini L, Pinti M, Nasi M, Montagna JP, De Biasi S, Roat E, et al. Quercetin and cancer chemoprevention. Evid Based Complement Alternat Med 2011;2011:591356. |
| 13. | Park MH, Min do S. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells. Biochem Biophys Res Commun 2011;412:710-5. |
| 14. | Du G, Lin H, Wang M, Zhang S, Wu X, Lu L, et al. Quercetin greatly improved therapeutic index of doxorubicin against 4T1 breast cancer by its opposing effects on HIF-1a in tumor and normal cells. Cancer Chemother Pharmacol 2010;65:277-87. |
| 15. | DiDonato JA, Mercurio F, Karin M. NF-kB and the link between inflammation and cancer. Immunol Rev 2012;246:379-400. |
| 16. | Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer 2002;2:301-10. |
| 17. | Perkins ND. The diverse and complex roles of NF-kB subunits in cancer. Nat Rev Cancer 2012;12:121-32. |
| 18. | Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell 2002;109 Suppl:S81-96. |
| 19. | Kanarek N, Ben-Neriah Y. Regulation of NF-kB by ubiquitination and degradation of the IkBs. Immunol Rev 2012;246:77-94. |
| 20. | Nakanishi C, Toi M. Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nat Rev Cancer 2005;5:297-309. |
| 21. | Sasaki N, Morisaki T, Hashizume K, Yao T, Tsuneyoshi M, Noshiro H, et al. Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue. Clin Cancer Res 2001;7:4136-42. |
| 22. | Wu L, Pu Z, Feng J, Li G, Zheng Z, Shen W. The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma. J Surg Oncol 2008;97:439-44. |
| 23. | Kang MJ, Ryu BK, Lee MG, Han J, Lee JH, Ha TK, et al. NF-kappaB activates transcription of the RNA-binding factor HuR, via PI3K-AKT signaling, to promote gastric tumorigenesis. Gastroenterology 2008;135:2030-42, 2042.e1. |
| 24. | Liu CA, Wang MJ, Chi CW, Wu CW, Chen JY. Rho/Rhotekin-mediated NF-kappaB activation confers resistance to apoptosis. Oncogene 2004;23:8731-42. |
| 25. | Sakamoto K, Hikiba Y, Nakagawa H, Hayakawa Y, Yanai A, Akanuma M, et al. Inhibitor of kappaB kinase beta regulates gastric carcinogenesis via interleukin-1alpha expression. Gastroenterology 2010;139:226-38.e6. |
| 26. | Matsumoto Y, Marusawa H, Kinoshita K, Endo Y, Kou T, Morisawa T, et al. Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med 2007;13:470-6. |
| 27. | Liu X, Wang X, Zhang J, Lam EK, Shin VY, Cheng AS, et al. Warburg effect revisited: An epigenetic link between glycolysis and gastric carcinogenesis. Oncogene 2010;29:442-50. |
| 28. | Cho SJ, Park JW, Kang JS, Kim WH, Juhnn YS, Lee JS, et al. Nuclear factor-kappaB dependency of doxorubicin sensitivity in gastric cancer cells is determined by manganese superoxide dismutase expression. Cancer Sci 2008;99:1117-24. |
| 29. | Zanotto-Filho A, Braganhol E, Schröder R, de Souza LH, Dalmolin RJ, Pasquali MA, et al. NFêB inhibitors induce cell death in glioblastomas. Biochem Pharmacol 2011;81:412-24.
|
| 30. | Meng Z, Lou S, Tan J, Xu K, Jia Q, Zheng W. Nuclear factor-kappa B inhibition can enhance apoptosis of differentiated thyroid cancer cells induced by 131I. PLoS One 2012;7:e33597. |
| 31. | Li Q, Yu YY, Zhu ZG, Ji YB, Zhang Y, Liu BY, et al. Effect of NF-kappaB constitutive activation on proliferation and apoptosis of gastric cancer cell lines. Eur Surg Res 2005;37:105-10. |
| 32. | Zaidi SF, Yamamoto T, Refaat A, Ahmed K, Sakurai H, Saiki I, et al. Modulation of activation-induced cytidine deaminase by curcumin in Helicobacter pylori-infected gastric epithelial cells. Helicobacter 2009;14:588-95. |
| 33. | Oliver FJ, de la Rubia G, Rolli V, Ruiz-Ruiz MC, de Murcia G, Murcia JM. Importance of poly (ADP-ribose) polymerase and its cleavage in apoptosis. Lesson from an uncleavable mutant. J Biol Chem 1998;273:33533-9. |
| 34. | Lipton SA, Bossy-Wetzel E. Dueling activities of AIF in cell death versus survival: DNA binding and redox activity. Cell 2002;111:147-50. |
| 35. | Kurokawa M, Kornbluth S. Caspases and kinases in a death grip. Cell 2009;138:838-54. |
| 36. | Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell 2011;147:742-58. |
| 37. | Tait SW, Green DR. Mitochondria and cell death: Outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 2010;11:621-32. |
| 38. | Liang Y, Tian W, Ma X. Inhibitory effects of grape skin extract and resveratrol on fatty acid synthase. BMC Complement Altern Med 2013;13:361. |
| 39. | Fan H, Tian W, Ma X. Curcumin induces apoptosis of HepG2 cells via inhibiting fatty acid synthase. Target Oncol 2014;9:279-86. |
| 40. | Fuchs O. Transcription factor NF-kB inhibitors as single therapeutic agents or in combination with classical chemotherapeutic agents for the treatment of hematologic malignancies. Curr Mol Pharmacol 2010;3:98-122. |
| 41. | Kim HJ, Hawke N, Baldwin AS. NF-kappaB and IKK as therapeutic targets in cancer. Cell Death Differ 2006;13:738-47. |
| 42. | Murata T, Shimada M, Kadono H, Sakakibara S, Yoshino T, Masuda T, et al. Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 2: Improvement of in vitro activity. Bioorg Med Chem Lett 2004;14:4013-7. |
| 43. | Ziegelbauer K, Gantner F, Lukacs NW, Berlin A, Fuchikami K, Niki T, et al. A selective novel low-molecular-weight inhibitor of IkappaB kinase-beta (IKK-beta) prevents pulmonary inflammation and shows broad anti-inflammatory activity. Br J Pharmacol 2005;145:178-92. |
| 44. | Lam LT, Davis RE, Pierce J, Hepperle M, Xu Y, Hottelet M, et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling. Clin Cancer Res 2005;11:28-40. |
| 45. | Mitsiades CS, Mitsiades N, Hideshima T, Richardson PG, Anderson KC. Proteasome inhibition as a new therapeutic principle in hematological malignancies. Curr Drug Targets 2006;7:1341-7. |
| 46. | Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T, et al. Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Biol Chem 1997;272:21096-103. |
| 47. | Fernández-Majada V, Aguilera C, Villanueva A, Vilardell F, Robert-Moreno A, Aytés A, et al. Nuclear IKK activity leads to dysregulated notch-dependent gene expression in colorectal cancer. Proc Natl Acad Sci U S A 2007;104:276-81. |
| 48. | Hernández-Vargas H, Rodríguez-Pinilla SM, Julián-Tendero M, Sánchez-Rovira P, Cuevas C, Antón A, et al. Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat 2007;102:157-72. |
| 49. | Keller SA, Schattner EJ, Cesarman E. Inhibition of NF-kappaB induces apoptosis of KSHV-infected primary effusion lymphoma cells. Blood 2000;96:2537-42. |
| 50. | Mori N, Yamada Y, Ikeda S, Yamasaki Y, Tsukasaki K, Tanaka Y, et al. Bay 11-7082 inhibits transcription factor NF-kappaB and induces apoptosis of HTLV-I-infected T-cell lines and primary adult T-cell leukemia cells. Blood 2002;100:1828-34. |
| 51. | Pickering BM, de Mel S, Lee M, Howell M, Habens F, Dallman CL, et al. Pharmacological inhibitors of NF-kappaB accelerate apoptosis in chronic lymphocytic leukaemia cells. Oncogene 2007;26:1166-77. |
| 52. | Catz SD, Johnson JL. Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 2001;20:7342-51. |
| 53. | Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: Balancing life and death - A new approach to cancer therapy. J Clin Invest 2005;115:2625-32. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
| This article has been cited by | | 1 |
Molecular and cellular outcomes of quercetin actions on healthy and tumor osteoblasts |
|
| Virginia Lezcano, Susana Morelli, Verónica González-Pardo | | Biochimie. 2022; 199: 46 | | [Pubmed] | [DOI] | | | 2 |
KCNQ Potassium Channels as Targets of Botanical Folk Medicines |
|
| Kaitlyn E. Redford, Geoffrey W. Abbott | | Annual Review of Pharmacology and Toxicology. 2022; 62(1): 447 | | [Pubmed] | [DOI] | | | 3 |
Is Quercetin Beneficial for Colon Cancer? A Cell Culture Study, Using the Apoptosis Pathways |
|
| Meltem Özgöçmen, Dilek Bayram, Ilkay Armagan, Gülçin Yavuz Türel, Murat Sevimli, Nurgül Senol | | Anti-Cancer Agents in Medicinal Chemistry. 2022; 22(1): 193 | | [Pubmed] | [DOI] | | | 4 |
Application of Quercetin in the Treatment of Gastrointestinal Cancers |
|
| Seyed Mohammad Ali Mirazimi, Fatemeh Dashti, Mohammad Tobeiha, Ali Shahini, Raha Jafari, Mehrad Khoddami, Amir Hossein Sheida, Parastoo EsnaAshari, Amir Hossein Aflatoonian, Fateme Elikaii, Melika Sadat Zakeri, Michael R Hamblin, Mohammad Aghajani, Minoodokht Bavarsadkarimi, Hamed Mirzaei | | Frontiers in Pharmacology. 2022; 13 | | [Pubmed] | [DOI] | | | 5 |
Valorization of Onion Waste by Obtaining Extracts Rich in Phenolic Compounds and Feasibility of Its Therapeutic Use on Colon Cancer |
|
| Mónica Paesa, Danielle Pires Nogueira, Gustavo Velderrain-Rodríguez, Irene Esparza, Nerea Jiménez-Moreno, Gracia Mendoza, Jesús Osada, Olga Martin-Belloso, María Jesús Rodríguez-Yoldi, Carmen Ancín-Azpilicueta | | Antioxidants. 2022; 11(4): 733 | | [Pubmed] | [DOI] | | | 6 |
Mechanistic Basis for the Role of Phytochemicals in Inflammation-Associated Chronic Diseases |
|
| Brianna Cote, Fawzy Elbarbry, Fiona Bui, Joe W. Su, Karen Seo, Arthur Nguyen, Max Lee, Deepa A. Rao | | Molecules. 2022; 27(3): 781 | | [Pubmed] | [DOI] | | | 7 |
A Comprehensive View on the Quercetin Impact on Colorectal Cancer |
|
| Andreea-Adriana Neamtu, Teodor-Andrei Maghiar, Amina Alaya, Neli-Kinga Olah, Violeta Turcus, Diana Pelea, Bogdan Dan Totolici, Carmen Neamtu, Adrian Marius Maghiar, Endre Mathe | | Molecules. 2022; 27(6): 1873 | | [Pubmed] | [DOI] | | | 8 |
Grape Pomace Extract Attenuates Inflammatory Response in Intestinal Epithelial and Endothelial Cells: Potential Health-Promoting Properties in Bowel Inflammation |
|
| Nadia Calabriso, Marika Massaro, Egeria Scoditti, Tiziano Verri, Amilcare Barca, Carmela Gerardi, Giovanna Giovinazzo, Maria Annunziata Carluccio | | Nutrients. 2022; 14(6): 1175 | | [Pubmed] | [DOI] | | | 9 |
Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy |
|
| Cristina Adriana Dehelean, Iasmina Marcovici, Codruta Soica, Marius Mioc, Dorina Coricovac, Stela Iurciuc, Octavian Marius Cretu, Iulia Pinzaru | | Molecules. 2021; 26(4): 1109 | | [Pubmed] | [DOI] | | | 10 |
Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways |
|
| Saleh A. Almatroodi, Mohammed A. Alsahli, Ahmad Almatroudi, Amit Kumar Verma, Abdulaziz Aloliqi, Khaled S. Allemailem, Amjad Ali Khan, Arshad Husain Rahmani | | Molecules. 2021; 26(5): 1315 | | [Pubmed] | [DOI] | | | 11 |
Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer |
|
| Aline Yammine, Amira Namsi, Dominique Vervandier-Fasseur, John J. Mackrill, Gérard Lizard, Norbert Latruffe | | Molecules. 2021; 26(12): 3483 | | [Pubmed] | [DOI] | | | 12 |
Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-?B Pathway/miR-146a Expression Modulation |
|
| Reda F. A. Abdelhameed, Amany K. Ibrahim, Mahmoud A. Elfaky, Eman S. Habib, Mayada I. Mahamed, Eman T. Mehanna, Khaled M. Darwish, Dina M. Khodeer, Safwat A. Ahmed, Sameh S. Elhady | | Antioxidants. 2021; 10(11): 1713 | | [Pubmed] | [DOI] | | | 13 |
Genomic Landscape of Head and Neck Squamous Cell Carcinoma Across Different Anatomic Sites in Chinese Population |
|
| Yunhe Ju, Xingrao Wu, Huizhen Wang, Bin Li, Qing Long, Dadong Zhang, Hao Chen, Nianqing Xiao, Fugen Li, Shiwen Zhang, Shenggang Yang | | Frontiers in Genetics. 2021; 12 | | [Pubmed] | [DOI] | | | 14 |
Positive Synergistic Effects of Quercetin and Rice Bran on Human Gut Microbiota Reduces Enterobacteriaceae Family Abundance and Elevates Propionate in a Bioreactor Model |
|
| Sudeep Ghimire, Supapit Wongkuna, Ranjini Sankaranarayanan, Elizabeth P. Ryan, G. Jayarama Bhat, Joy Scaria | | Frontiers in Microbiology. 2021; 12 | | [Pubmed] | [DOI] | | | 15 |
The High Content of Quercetin and Catechin in Airen Grape Juice Supports Its Application in Functional Food Production |
|
| Daniel J. García-Martínez, María Arroyo-Hernández, María Posada-Ayala, Cruz Santos | | Foods. 2021; 10(7): 1532 | | [Pubmed] | [DOI] | | | 16 |
Quercetin Offers Chemopreventive Potential against Breast Cancer by Targeting a Network of Signalling Pathways |
|
| Hanaa H. Ahmed, Hadeer A. Aglan, Ghada H. Elsayed, Hebatallah G. Hafez, Emad F. Eskander | | Research Journal of Pharmacy and Technology. 2021; : 2829 | | [Pubmed] | [DOI] | | | 17 |
Mangifera indica (Mango): A Promising Medicinal Plant for Breast Cancer Therapy and Understanding Its Potential Mechanisms of Action |
|
| Kah Min Yap, Mahendran Sekar, Lay Jing Seow, Siew Hua Gan, Srinivasa Reddy Bonam, Nur Najihah Izzati Mat Rani, Pei Teng Lum, Vetriselvan Subramaniyan, Yuan Seng Wu, Neeraj Kumar Fuloria, Shivkanya Fuloria | | Breast Cancer: Targets and Therapy. 2021; Volume 13: 471 | | [Pubmed] | [DOI] | | | 18 |
A Comprehensive Overview of Colon Cancer- A Grim Reaper of the 21st Century |
|
| Rajesh Kumar, Seetha Harilal, Simone Carradori, Bijo Mathew | | Current Medicinal Chemistry. 2021; 28(14): 2657 | | [Pubmed] | [DOI] | | | 19 |
Investigating the Mechanism of Scutellariae barbata Herba in the Treatment of Colorectal Cancer by Network Pharmacology and Molecular Docking |
|
| Xiangjun Qi, Hongbin Xu, Peng Zhang, Guoming Chen, Zhiqiang Chen, Caishan Fang, Lizhu Lin, Ching-Liang Hsieh | | Evidence-Based Complementary and Alternative Medicine. 2021; 2021: 1 | | [Pubmed] | [DOI] | | | 20 |
Dietary polyphenols in chemoprevention and synergistic effect in cancer: Clinical evidences and molecular mechanisms of action |
|
| Srimanta Patra, Biswajita Pradhan, Rabindra Nayak, Chhandashree Behera, Surajit Das, Samir Kumar Patra, Thomas Efferth, Mrutyunjay Jena, Sujit Kumar Bhutia | | Phytomedicine. 2021; 90: 153554 | | [Pubmed] | [DOI] | | | 21 |
The Phytochemical Profile and Biological Activity of Liquidambar orientalis Mill. var. orientalis via NF-?B and Apoptotic Pathways in Human Colorectal Cancer |
|
| Sümeyra Çetinkaya, Ilknur Çinar Ayan, Ipek Süntar, Hatice Gül Dursun | | Nutrition and Cancer. 2021; : 1 | | [Pubmed] | [DOI] | | | 22 |
Bavachinin mitigates DMH induced colon cancer in rats by altering p53/Bcl2/BAX signaling associated with apoptosis |
|
| Chun Zhao, Balaram Ghosh, Tania Chakraborty, Souvik Roy | | Biotechnic & Histochemistry. 2021; 96(3): 179 | | [Pubmed] | [DOI] | | | 23 |
Polymeric Nanocarriers: a Promising Tool for Early Diagnosis and Efficient Treatment of Colorectal Cancer |
|
| Mohamed Haider, Haidy Osama Ibrahim, Khalid Zaki Zaki, Mariam Rafat El Hamshary, Gorka Orive, Zahid Hussain | | Journal of Advanced Research. 2021; | | [Pubmed] | [DOI] | | | 24 |
Nano-encapsulated quercetin by soluble soybean polysaccharide/chitosan enhances anti-cancer, anti-inflammation, and anti-oxidant activities |
|
| Hyunjin Moon, Pattawika Lertpatipanpong, Yukyung Hong, Chong-Tai Kim, Seung Joon Baek | | Journal of Functional Foods. 2021; 87: 104756 | | [Pubmed] | [DOI] | | | 25 |
Curcuma as an adjuvant in colorectal cancer treatment |
|
| Cecilia Villegas, Rebeca Perez, Olov Sterner, Iván González-Chavarría, Cristian Paz | | Life Sciences. 2021; 286: 120043 | | [Pubmed] | [DOI] | | | 26 |
Posttranslational modifications as therapeutic targets for intestinal disorders |
|
| Jieun Choo, Gwangbeom Heo, Charalabos Pothoulakis, Eunok Im | | Pharmacological Research. 2021; 165: 105412 | | [Pubmed] | [DOI] | | | 27 |
A review on the molecular mechanisms, the therapeutic treatment including the potential of herbs and natural products, and target prediction of obesity-associated colorectal cancer |
|
| Huihai Yang, Grace Gar Lee Yue, Ping Chung Leung, Chun Kwok Wong, Clara Bik San Lau | | Pharmacological Research. 2021; : 106031 | | [Pubmed] | [DOI] | | | 28 |
Incorporation of natural assumption to deal with cancer |
|
| Chenmala Karthika, Raman Sureshkumar | | Environmental Science and Pollution Research. 2021; 28(5): 4902 | | [Pubmed] | [DOI] | | | 29 |
Network Pharmacology-Based Study on the Mechanism of Gegen Qinlian Decoction against Colorectal Cancer |
|
| Qiaowei Fan, Lin Guo, Jingming Guan, Jing Chen, Yujing Fan, Zhendong Chen, Hulun Li, Shao Li | | Evidence-Based Complementary and Alternative Medicine. 2020; 2020: 1 | | [Pubmed] | [DOI] | | | 30 |
Cedrus deodara (Bark) Essential Oil Induces Apoptosis in Human Colon Cancer Cells by Inhibiting Nuclear Factor kappa B |
|
| Madhulika Bhagat, Ajay Kumar, Renuka Suravajhala | | Current Topics in Medicinal Chemistry. 2020; 20(22): 1981 | | [Pubmed] | [DOI] | | | 31 |
In Silico Anticancer Evaluation, Molecular Docking and Pharmacophore Modeling of Flavonoids against Various Cancer Targets |
|
| Jainey Puthenveettil James, Pankaj Kumar, Abhishek Kumar, Katte Ishwar Bhat, Chakrakodi Shashidhara Shastry | | Letters in Drug Design & Discovery. 2020; 17(12): 1485 | | [Pubmed] | [DOI] | | | 32 |
Anticancer Effects of Fufang Yiliu Yin Formula on Colorectal Cancer Through Modulation of the PI3K/Akt Pathway and BCL-2 Family Proteins |
|
| Bingzi Dong, Zhenjie Yang, Qiang Ju, Shigao Zhu, Yixiu Wang, Hao Zou, Chuandong Sun, Chengzhan Zhu | | Frontiers in Cell and Developmental Biology. 2020; 8 | | [Pubmed] | [DOI] | | | 33 |
The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin |
|
| Gaber El-Saber Batiha, Amany Magdy Beshbishy, Muhammad Ikram, Zohair S. Mulla, Mohamed E. Abd El-Hack, Ayman E. Taha, Abdelazeem M. Algammal, Yaser Hosny Ali Elewa | | Foods. 2020; 9(3): 374 | | [Pubmed] | [DOI] | | | 34 |
Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation |
|
| Wamidh H. Talib, Izzeddin Alsalahat, Safa Daoud, Reem Fawaz Abutayeh, Asma Ismail Mahmod | | Molecules. 2020; 25(22): 5319 | | [Pubmed] | [DOI] | | | 35 |
Flavonoids Regulate Inflammation and Oxidative Stress in Cancer |
|
| Guangxing Li, Kaiyue Ding, Yanling Qiao, Liu Zhang, Luping Zheng, Taowen Pan, Lin Zhang | | Molecules. 2020; 25(23): 5628 | | [Pubmed] | [DOI] | | | 36 |
New Oleoyl Hybrids of Natural Antioxidants: Synthesis and In Vitro Evaluation as Inducers of Apoptosis in Colorectal Cancer Cells |
|
| Gabriele Carullo, Sarah Mazzotta, Adrian Koch, Kristin M. Hartmann, Oliver Friedrich, Daniel F. Gilbert, Margarita Vega-Holm, Regine Schneider-Stock, Francesca Aiello | | Antioxidants. 2020; 9(11): 1077 | | [Pubmed] | [DOI] | | | 37 |
Potential proapoptotic phytochemical agents for the treatment and prevention of colorectal cancer (Review) |
|
| Kanwal Ahmed, Syed Zaidi, Zheng-Guo Cui, Dejun Zhou, Sheikh Saeed, Hidekuni Inadera | | Oncology Letters. 2019; | | [Pubmed] | [DOI] | | | 38 |
The Effect of Aerobic Training with Purslane (Portulaca Oleracea) Seed on Toll Like Receptors in Colon Tumor Tissue of Adult Rats with Colon Cancer |
|
| Abdol Kheder Keshtvarz, Maghsoud Peeri, Mohammad Ali Azarbayjani, Seyed Ali Hosseini | | Jorjani Biomedicine Journal. 2019; 7(4): 49 | | [Pubmed] | [DOI] | | | 39 |
NF-?B targeting for overcoming tumor resistance and normal tissues toxicity |
|
| Keywan Mortezaee, Masoud Najafi, Bagher Farhood, Amirhossein Ahmadi, Dheyauldeen Shabeeb, Ahmed E. Musa | | Journal of Cellular Physiology. 2019; 234(10): 17187 | | [Pubmed] | [DOI] | | | 40 |
Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer |
|
| Saber G. Darband, Mojtaba Kaviani, Bahman Yousefi, Shirin Sadighparvar, Firouz G. Pakdel, Javad A. Attari, Iraj Mohebbi, Somayeh Naderi, Maryam Majidinia | | Journal of Cellular Physiology. 2018; 233(9): 6544 | | [Pubmed] | [DOI] | | | 41 |
Quercetin attenuates zymosan-induced arthritis in mice |
|
| Carla F.S. Guazelli, Larissa Staurengo-Ferrari, Ana C. Zarpelon, Felipe A. Pinho-Ribeiro, Kenji W. Ruiz-Miyazawa, Fabiana T.M.C. Vicentini, Josiane A. Vignoli, Doumit Camilios-Neto, Sandra R. Georgetti, Marcela M. Baracat, Rubia Casagrande, Waldiceu A. Verri | | Biomedicine & Pharmacotherapy. 2018; 102: 175 | | [Pubmed] | [DOI] | | | 42 |
Cilostazol and enzymatically modified isoquercitrin attenuate experimental colitis and colon cancer in mice by inhibiting cell proliferation and inflammation |
|
| Yumi Kangawa,Toshinori Yoshida,Kiyoshi Maruyama,Minako Okamoto,Tohru Kihara,Michi Nakamura,Masako Ochiai,Yoshitaka Hippo,Shim-mo Hayashi,Makoto Shibutani | | Food and Chemical Toxicology. 2017; 100: 103 | | [Pubmed] | [DOI] | | | 43 |
Differential cytotoxic activity of Quercetin on colonic cancer cells depends on ROS generation through COX-2 expression |
|
| Subramaniya Bharathi Raja,Vijayabharathi Rajendiran,Nirmal Kumar Kasinathan,Amrithalakshmi P,Sivaramakrishnan Venkatabalasubramanian,Malliga Raman Murali,Halagowder Devaraj,Sivasithamparam Niranjali Devaraj | | Food and Chemical Toxicology. 2017; 106: 92 | | [Pubmed] | [DOI] | | | 44 |
Inhibition of Mahkota Dewa (Phaleria macrocarpa) bioactive fraction on proliferation of human retinoblastoma tumor cells Y-79 through suppression of mRNA level of cyclin E |
|
| Nugroho Trilaksana,Ignatius Riwanto,Raymond Rubianto Tjandrawinata,Reki Winarto | | Asian Pacific Journal of Tropical Biomedicine. 2017; | | [Pubmed] | [DOI] | | | 45 |
Friend or foe? |
|
| Tommaso Colangelo,Giovanna Polcaro,Livio Muccillo,Giovanna DæAgostino,Valeria Rosato,Pamela Ziccardi,Angelo Lupo,Gianluigi Mazzoccoli,Lina Sabatino,Vittorio Colantuoni | | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 2017; 1867(1): 1 | | [Pubmed] | [DOI] | | | 46 |
Synergism of co-delivered nanosized antioxidants displayed enhanced anticancer efficacy in human colon cancer cell lines |
|
| Lipika Ray,Manish Kumar Pal,Ratan Singh Ray | | Bioactive Materials. 2017; | | [Pubmed] | [DOI] | | | 47 |
Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma |
|
| Yock Ping Chow,Lu Ping Tan,San Jiun Chai,Norazlin Abdul Aziz,Siew Woh Choo,Paul Vey Hong Lim,Rajadurai Pathmanathan,Noor Kaslina Mohd Kornain,Chee Lun Lum,Kin Choo Pua,Yoke Yeow Yap,Tee Yong Tan,Soo Hwang Teo,Alan Soo-Beng Khoo,Vyomesh Patel | | Scientific Reports. 2017; 7: 42980 | | [Pubmed] | [DOI] | | | 48 |
Pengaruh Ekstrak Etanol Daun Kelor (Moringa Oleifera Lam.) Terhadap Jumlah Sel Mast Pada Mencit(Mus Musculus) Model Endometriosis |
|
| Dina Novarita Kusuma Wardani | | Jurnal Biosains Pascasarjana. 2017; 19(3): 260 | | [Pubmed] | [DOI] | | | 49 |
Shaping functional gut microbiota using dietary bioactives to reduce colon cancer risk |
|
| Derek V. Seidel,M. Andrea Azcárate-Peril,Robert S. Chapkin,Nancy D. Turner | | Seminars in Cancer Biology. 2017; | | [Pubmed] | [DOI] | | | 50 |
Inhibitory Effects of Quercetin on Progression of Human Choriocarcinoma Cells Are Mediated Through PI3K/AKT and MAPK Signal Transduction Cascades |
|
| Whasun Lim,Changwon Yang,Sunwoo Park,Fuller W. Bazer,Gwonhwa Song | | Journal of Cellular Physiology. 2016; | | [Pubmed] | [DOI] | | | 51 |
Purified rutin and rutin-rich asparagus attenuates disease severity and tissue damage following dextran sodium sulfate-induced colitis |
|
| Krista A. Power,Jenifer T. Lu,Jennifer M. Monk,Dion Lepp,Wenqing Wu,Claire Zhang,Ronghua Liu,Rong Tsao,Lindsay E. Robinson,Geoffrey A. Wood,David J. Wolyn | | Molecular Nutrition & Food Research. 2016; | | [Pubmed] | [DOI] | | | 52 |
Inhibitory effect of quercetin on colorectal lung metastasis through inducing apoptosis, and suppression of metastatic ability |
|
| Ji-Ye Kee,Yo-Han Han,Dae-Seung Kim,Jeong-Geon Mun,Jinbong Park,Mi-Young Jeong,Jae-Young Um,Seung-Heon Hong | | Phytomedicine. 2016; 23(13): 1680 | | [Pubmed] | [DOI] | | | 53 |
Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals |
|
| Chuan LI,Jia ZHANG,Yu-Jiao ZU,Shu-Fang NIE,Jun CAO,Qian WANG,Shao-Ping NIE,Ze-Yuan DENG,Ming-Yong XIE,Shu WANG | | Chinese Journal of Natural Medicines. 2015; 13(9): 641 | | [Pubmed] | [DOI] | |
|
 |
|
|
|
