Home | About PM | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Pharmacognosy Magazine
Search Article 
  
Advanced search 
 

 
  Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 75  |  Page : 539-544  

Curcumin Mediates the Proliferation and Apoptosis of Colorectal Cancer Cells by Downregulating the Expression of Interleukin-1β through the Nuclear Factor-κB Signaling Pathway


1 Department of Geriatrics, Taizhou People's Hospital, Taizhou 225300, Jiangsu, China
2 Department of Oncology, Taizhou People's Hospital, Taizhou 225300, Jiangsu, China
3 Department of General Surgery, Taizhou People's Hospital, Taizhou 225300, Jiangsu, China

Date of Submission27-Oct-2019
Date of Decision06-Dec-2019
Date of Acceptance03-Dec-2020
Date of Web Publication11-Nov-2021

Correspondence Address:
Changhe Zhang
Department of General Surgery, Taizhou People's Hospital, Hailing South Road No. 399, Taizhou 225300, Jiangsu
China
Xiaowu Qian
Department of Geriatrics, Taizhou People's Hospital, Hailing South Road No. 399, Taizhou 225300, Jiangsu
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_388_19

Rights and Permissions
   Abstract 


Background: Colorectal cancer (CRC) is a frequently occurring malignant tumor, which is mainly observed in elderly men with no significant symptoms at the early stage. Among the malignant tumors of the digestive system, the incidence and mortality of CRC rank second only to hepatic and gastric cancer. Curcumin is an antioxidant and anti-inflammatory compound extracted from the roots of Curcuma longa plant. The antitumor effects of curcumin have been widely reported for various types of cancers, including CRC. Objective: In this study, we aimed to elucidate the protective effects and mechanism of interleukin (IL)-1 β on curcumin-induced apoptosis in SW480 cells. Materials and Methods: Expression levels of IL-1 β in CRC tissues and cells were detected by the quantitative reverse transcription polymerase chain reaction and Western blot assays. Followed by the incubation of cells with curcumin, the effect on IL-1 β was measured. Moreover, after transfection, the effects of IL-1 β on curcumin-induced SW480 cellular processes were analyzed by cell counting kit-8 and flow cytometric analysis. Results: According to the results of this study, IL-1 β was significantly increased in CRC tissues and cells. However, after incubation of the cells with curcumin, IL-1 β was downregulated and overexpression of IL-1 β counteracted the antitumor functions of curcumin in SW480 cells. Further studies have shown that curcumin could promote apoptosis of SW480 cells by inhibiting nuclear factor-κB (NF-κB) signaling pathway. Conclusion: Our study validated that curcumin inhibits SW480 cell proliferation but promotes apoptosis by downregulating the expression of IL-1 β probably through NF-κB signaling pathway. IL-1 β may an important target for the treatment of CRC.

Keywords: Colorectal cancer, curcumin, interleukin-1 beta, nuclear factor-κB pathway


How to cite this article:
Qian X, Jiang C, Zhu Z, Han G, Wang R, Zhang C. Curcumin Mediates the Proliferation and Apoptosis of Colorectal Cancer Cells by Downregulating the Expression of Interleukin-1β through the Nuclear Factor-κB Signaling Pathway. Phcog Mag 2021;17:539-44

How to cite this URL:
Qian X, Jiang C, Zhu Z, Han G, Wang R, Zhang C. Curcumin Mediates the Proliferation and Apoptosis of Colorectal Cancer Cells by Downregulating the Expression of Interleukin-1β through the Nuclear Factor-κB Signaling Pathway. Phcog Mag [serial online] 2021 [cited 2021 Dec 1];17:539-44. Available from: http://www.phcog.com/text.asp?2021/17/75/539/330211



SUMMARY

  • Curcumin, a well-known phytochemical, is the bioactive pigment of turmeric which has a variety of pharmacological activities. Curcumin is a familiar and effective anticancer component in the field of cancer, including colorectal cancer (CRC). Cumulative evidence supports the fact that inflammatory factors such as cytokines are key mediators involved in regulating the growth of CRC. Interleukin (IL)-1β, a crucial member of the IL-1 family of cytokines, functioning as an important mediator in the inflammatory response while playing a vital role in many cellular activities, including cell proliferation, apoptosis, and differentiation. IL-1β has been thought to be associated with CRC progression and development. Meanwhile, other studies have pointed out that inhibition of nuclear factor-κB (NF-κB) signaling pathway may promote cancer cell apoptosis and restrain proliferation in CRC.
  • In this study, we found that IL-1β was significantly increased in CRC tumor tissues and cells. After incubating with curcumin, the expression level of IL-1 β was significantly decreased. Moreover, curcumin suppressed SW480 cell proliferation but promoted apoptosis by inhibition of IL-1β through the NF-κB signaling pathway.




Abbreviations used: CRC: Colorectal Cancer; IL-1β, Interleukin-1β; NF-κB: Nuclear Factor-κB


   Introduction Top


Colorectal cancer (CRC) is the third most common type of cancer worldwide,[1] and its morbidity ranks second in China.[2] To date, treatment modalities used for CRC include surgery, radiation therapy, chemotherapy, and targeted therapy.[3] However, due to the characteristics of high recurrence and poor prognosis, the clinical treatment effect of CRC is greatly compromised.

Curcumin, a well-known phytochemical, is the bioactive pigment of turmeric which has a variety of pharmacological activities.[4] It is a potential cure for several diseases. For instance, curcumin is used as a cardioprotective agent for the treatment of myocardial ischemia.[5] A recent report suggests that curcumin shows beneficial effects on hepatic injury and cirrhosis.[6] Curcumin is a familiar and effective anticancer component in the field of cancer.[7] Prior studies demonstrate the effectiveness of curcumin against different types of tumors,[8],[9],[10] including CRC.[11] However, the detailed mechanisms of curcumin-mediated CRC progression remain unclear.

Cumulative evidence supports the fact that inflammatory factors such as cytokines are key mediators involved in regulating the growth of CRC.[12],[13] Interleukin (IL)-1 β, a crucial member of the IL-1 family of cytokines, functioning as an important mediator in the inflammatory response while playing a vital role in many cellular activities, including cell proliferation, apoptosis, and differentiation.[14],[15] IL-1 β has been thought to be associated with CRC progression and development.[16] A previous study revealed that IL-1 β may exert inflammatory activities by activating NK-κB signaling in CRC.[17] Meanwhile, other studies have pointed out that inhibition of nuclear factor-κB (NF-κB) signaling pathway may promote cancer cell apoptosis and restrain proliferation in CRC.[18],[19],[20] However, the underlying mechanisms of IL-1 β/NF-κB axis regulated by curcumin in the CRC micro-environment are not fully understood.

In this study, we found that IL-1 β was significantly increased in CRC tumor tissues and cells. After incubating with curcumin, the expression level of IL-1 β was significantly decreased. Moreover, curcumin suppressed SW480 cell proliferation but promoted apoptosis by inhibition of IL-1 β through the NF-κB signaling pathway.


   Materials and Methods Top


Samples

A total of 30 pairs of CRC samples and their matched adjacent normal samples were collected between June 2015 and September 2017 at the Taizhou People's Hospital (Hailing South Road No. 399, Taizhou 225300, Jiangsu, China) and preserved in liquid nitrogen. All samples were obtained from patients with CRC who had undergone surgical resections without undergoing any chemotherapy, radiation, or other adjuvant therapy. The protocol of this study was approved by the Ethics Committee of Taizhou People's Hospital and informed consent was obtained from each patient.

Cell culture

The HCoEpiC, HT29, HCT116, and SW480 cell lines were purchased from Shanghai Institution for Biological Sciences (Shanghai, China) and cultured in Dulbecco's Modified Eagle medium (DMEM; Gibco, CA, USA) with 10% fetal bovine serum (FBS; Hyclone, Shanghai, China) containing penicillin/streptomycin at 37°C in a humidified incubator with 5% CO2.

Cell viability assay

Cell viability was measured using Cell Counting Kit-8 (CCK-8 kit; Beyotime, Hangzhou, China). Briefly, SW480 cells were seeded in a 96-plate well at a density of 0.5 × 104 cells/well under a humidified atmosphere containing 5% CO2 at 37°C. Following this, 20 μM curcumin and IL-1 β (Recombinant Human IL-1 β; LT-0111-010; 10 ng/mL) were added to the plate and further incubated for 24, 48, and 72 h, respectively. CCK-8 reagent was added into each well, and the culture was carried out for another 50 min. The absorbance of each well was read at 490 nm using a microplate reader (TECAN Infinite M1000; TECAN, Shanghai, China).

Annexin V-FITC/PI double staining assay

The cell apoptosis rate was determined using an Annexin V-FITC/PI apoptosis kit (Dojindo Molecular Technologies, Inc., Kumamoto, Japan) according to the manufacturer's protocol. Briefly, the cells were seeded at a density of 1 × 105 cells/well in a six-well plate and treated with 20 μM curcumin and IL-1 β. After 24 h of incubation, the cells were harvested by centrifugation at 1000 rpm for 5 min and stained with propidium iodide and Annexin V. FACSCalibur (BD Bioscience, Shanghai, China) was used to analyze the apoptotic cells.

Protein extraction and western blotting

Total protein was extracted from the tissues and cells using radioimmunoprecipitation assay (Solarbio, Beijing, China) buffer. Following this, the protein content was determined using a bicinchoninic acid protein assay kit according to the manufacturer's instructions. The proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred onto a PVDF membrane, which was blocked in 5% non-fat milk for 50 min. The membranes were incubated at 4°C overnight with primary antibodies (IL-1 β, Bcl-2, phosphate-NF-κB, Bax, Caspase-3, and GAPDH), whereas GAPDH functioned as the endogenous control for protein loading. Afterward, the membranes were incubated at 37°C for another 2 h with horseradish peroxidase-conjugated secondary antibodies followed by ECL Western blotting detection reagent (Thermo Fisher Scientific, Rockford, IL, USA). Data were analyzed using Image Lab software (BioRad Laboratories, CA, USA).

RNA isolation and quantitative reverse transcription polymerase chain reaction

Total RNA was extracted with TRIzol reagent (Invitrogen, CA, USA). All primers were designed and synthesized by Genscript (Nanjing, China) according to the manufacturer's instructions. Subsequently, RNA was reverse transcribed into cDNA with SuperScript reagent (Invitrogen, MA, USA). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed with TaqMan PCR reagent kit (Applied Biosystems, NJ, USA) as per the manufacturer's instructions. The reaction procedure was as follows: 52°C for 2 min, 94°C for 10 min; 30 cycles of 94°C for 10 s, and 52°C for 30 s. GAPDH was used as an endogenous control. The expression level of IL-1 β in CRC tissues was measured according to the 2−△△Ct method.

Statistical analysis

All the results were presented as mean ± standard deviation. SPSS software version 19.0 (SPSS Inc., Chicago, IL, USA) was used to analyze the data. Significant differences among the groups were evaluated by the Student's t-test or one-way analysis of variance followed by the Newman–Keuls method. P < 0.05 was considered statistically significant.


   Results Top


The expression level of interleukin-1 β is upregulated in colorectal cancer tissues

Through RT-qPCR and Western blot assays, the expression of IL-1 β in 30 sets of paired tissues was determined. As demonstrated in [Figure 1]a, a remarkably high level of IL-1 β mRNA and protein was found in the CRC tissues [Figure 1]b.
Figure 1: Interleukin-1 β expressions were up-regulated in colorectal cancer samples. (a) Significantly higher mRNA levels of interleukin-1 β expression were found in the colorectal tumor samples compared with adjacent non-tumor samples (P < 0.01). (b) Significantly higher protein levels of interleukin-1 β expression were found in the colorectal tumor samples compared with adjacent nontumor samples. **P < 0.01, tumor versus control

Click here to view


Curcumin suppresses the expression of interleukin-1 β in SW480 cells

To corroborate the basic function of curcumin on IL-1 β expression, we first detected the expression of IL-1 β in four cell lines. As demonstrated in [Figure 2]a, a significantly high level of expression of IL-1 β was measured in SW480 cell lines. After treatment with 20 μM curcumin, the expression of IL-1 β mRNA and protein was significantly [Figure 2]b and [Figure 2]c.
Figure 2: Curcumin inhibits the expression levels of interleukin-1 β in colorectal cancer cells. (a) Significantly higher expression levels of interleukin-1 β were found in SW480 cells. (b) Curcumin inhibits the mRNA expression levels of interleukin-1 β in SW480 cells (P < 0.01). (c) Curcumin inhibits the protein expression levels of interleukin-1 β in SW480 cells. **P < 0.01, curcumin versus control

Click here to view


Curcumin suppresses SW480 cell proliferation by inhibition of interleukin-1 β expression

In this study, the CCK-8 assay was performed to detect the proliferation of SW480 cells. As demonstrated in [Figure 3], the proliferation of SW480 cells was remarkably decreased after treatment with curcumin. However, the reduction in proliferation was partially reversed by the upregulation of IL-1 β expression.
Figure 3: Curcumin inhibits SW480 cell proliferation by decreasing interleukin-1 β expression. The cell viability of SW480 measured by cell counting kit-8 assay in different groups. **P < 0.01, *P < 0.05, interleukin-1 β versus control, curcumin versus control, interleukin-1 β + Curcumin versus interleukin-1 β

Click here to view


Curcumin promotes SW480 cell apoptosis by inhibition of interleukin-1 β expression through the nuclear factor-κB signaling pathway

To demonstrate the effects of curcumin on SW480 cell apoptosis, we performed flow cytometry and Western blot analysis. As demonstrated in [Figure 4], curcumin-induced apoptosis in SW480 cells could be reversed by increasing the expression of IL-1 β. Furthermore, after treatment with curcumin, the expression levels of IL-1 β, Bcl-2, and p-p65 were significantly downregulated, whereas the expression level of Bax and Caspase-3 were upregulated [Figure 5]. However, the variation of Bcl-2, p-p65, Bax, and Caspase-3 induced by curcumin could be partially counteracted by IL-1 β
Figure 4: Curcumin promotes SW480 cell apoptosis by decreasing interleukin-1 β expression. (a) Control group; (b) interleukin-1 β group; (c) Curcumin group; (d) interleukin-1 β + curcumin group

Click here to view
Figure 5: Curcumin increases interleukin-1 β expression via nuclear factor-κB signaling pathway. (a) Expressions of interleukin-1 β and apoptosis-related factors measured by western blot assay. (b) Quantified results of A were presented. (c) Expressions of p-p65 measured by western blot assay. (d) Quantified results of C were presented. **P < 0.01, *P < 0.05, interleukin-1 β versus control, Curcumin versus control, interleukin-1 β + Curcumin versus interleukin-1 β

Click here to view



   Discussion Top


IL-1 β, a primary pro-inflammatory cytokine, functions as a pleiotropic agent in tumorigenesis, tumor growth, and metastasis.[21],[22] Previous studies have shown that the expression of IL-1 β is elevated in CRC tissues,[23] which is compatible with the findings of this study, indicating that IL-1 β acts as an oncogene in CRC cells. In addition, in keeping with previous results, we were able to demonstrate that IL-1 β expression was suppressed by curcumin.[24],[25] Since curcumin is an upstream stimulator of IL-1 β in CRC in vitro, we further evaluated the functions of the curcumin/IL-1 β axis in the regulation of CRC cell progression. We found that curcumin may suppress proliferation but increase apoptosis of SW480 cells by the inhibition of IL-1 β, suggesting that IL-1 β functions as an oncogenic protein in CRC development.

Cumulative evidence highlighted the value of IL-1 β in the development of malignant types of cancer cells. For instance, the downregulation of expression of IL-1 β may suppress cell invasiveness in breast cancer.[26] As in CRC, IL-1 β promotes colon cancer cell growth as well as invasion.[27] Curcumin is widely used in ancient medicine and has been shown to induce cell apoptosis in CRC,[28] indicating its potential value as a tumor suppressor in CRC. In agreement with these reports, we found that IL-1 β may increase cell proliferation but inhibit apoptosis of CRC, the effect of which was reversed by curcumin.

Previous studies have shown that curcumin shows its antioxidant, anti-inflammatory, and anti-tumor properties by targeting specific signaling pathways such as NF-κB, Nrf2, and PTEN pathways.[29],[30],[31],[32] NF-κB is present in almost all animal cell types and plays a crucial role in regulating the immune response to infection.[33],[34] Previous studies have reported that abnormal regulation of the NF-κB signaling pathway is related to inflammatory and tumor progression.[35],[36] Furthermore, cumulative evidence has confirmed that its abnormal activation is a key factor in the progression of CRC.[37],[38] Accumulating evidence suggests that curcumin inhibits the NF-κB signaling pathway to regulate the cellular processes in cervical cancer,[39] squamous cell carcinoma,[40] esophageal cancer,[41] and breast cancer.[42] In this study, we found that the upregulation of IL-1 β markedly increased the expression level of Bcl-2 and p-p65 and decreased the expression level of Bcl-2, Bax, and Caspase; however, the variation could be reversed by curcumin. These results suggest that curcumin is involved in the regulation of growth and development of CRC by the inhibitory effect of IL-1 β through the NF-κB signaling pathway.

This study has some limitations. First, the sample size of our experiment is small and we need to recruit more participants in order to obtain more accurate results. Second, we will conduct further experiments by inhibiting IL-1 β expression to verify whether NF-κB is directly regulated by IL-1 β. Last but not the least, immunolabeling and in vivo experiments need to be conducted in the future.


   Conclusion Top


In general, our study elucidates the effects of curcumin as a crucial therapeutic option in CRC treatment. Furthermore, the overexpression of IL-1 β in CRC samples and cells could partially counteract the effect of curcumin in restoring the proliferation or promoting the apoptosis of SW480 cells. In summary, our study suggests that curcumin may regulate the proliferation and apoptosis of SW480 cells by the suppression of IL-1 β via NF-κB pathway.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Chen Y, Jiang J, Zhao M, Luo X, Liang Z, Zhen Y, et al. MicroRNA-374a suppresses colon cancer progression by directly reducing CCND1 to inactivate the PI3K/AKT pathway. Oncotarget 2016;7:41306-19.  Back to cited text no. 1
    
2.
Li L, Ma BB. Colorectal cancer in Chinese patients: Current and emerging treatment options. Onco Targets Ther 2014;7:1817-28.  Back to cited text no. 2
    
3.
Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet 2014;383:1490-502.  Back to cited text no. 3
    
4.
Ahmed S, Khan H, Mizaei. Mechanims insights of curcumin in myocardial ischemia: where are we standing? Eur J Med Chem 2019;183:111658.  Back to cited text no. 4
    
5.
Shafabakhsh R, Pourhanifeh MH, Mirzaei HR, Sahebkar A, Asemi Z, Mirzaei H, et al. Targeting regulatory T cells by curcumin: A potential for cancer immunotherapy. Pharmacol Res 2019;147:104353.  Back to cited text no. 5
    
6.
Nouri-Vaskeh M, Mahdavi AM, Afshan H, Alizadeh L, Zarei M. Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: A randomized controlled trial. Phytother Res 2020;34(6):1446-1454. [doi: 10.1002/ptr. 6620].  Back to cited text no. 6
    
7.
Bar-Sela G, Epelbaum R, Schaffer M. Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications. Curr Med Chem 2010;17:190-7.  Back to cited text no. 7
    
8.
Fu H, Wang C, Yang D, Wei Z, Xu J, Hu Z, et al. Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling. J Cell Physiol 2018;233:4634-42.  Back to cited text no. 8
    
9.
Zhu JY, Yang X, Chen Y, Jiang Y, Wang SJ, Li Y, et al. Curcumin suppresses lung cancer stem cells via inhibiting Wnt/β-catenin and sonic hedgehog pathway. Phytother Res 2017;31:680-8.  Back to cited text no. 9
    
10.
Lv ZD, Liu XP, Zhao WJ, Dong Q, Li FN, Wang HB, et al. Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo. Int J Clin Exp Pathol 2014;7:2818-24.  Back to cited text no. 10
    
11.
Li B, Shi C, Li B, Zhao JM, Wang L. The effects of curcumin on HCT-116 cells proliferation and apoptosis via the miR-491/PEG10 pathway. J Cell Biochem 2018;119:3091-8.  Back to cited text no. 11
    
12.
Hu WH, Chen HH, Yen SL, Huang HY, Hsiao CC, Chuang JH. Increased expression of interleukin-23 associated with progression of colorectal cancer. J Surg Oncol 2017;115:208-12.  Back to cited text no. 12
    
13.
Wu D, Wu P, Huang Q, Liu Y, Ye J, Huang J. Interleukin-17: a promoter in colorectal cancer progression. Clin Dev Immunol 2013;2013:436307.  Back to cited text no. 13
    
14.
Striz I. Cytokines of the IL-1 family: Recognized targets in chronic inflammation underrated in organ transplatations. Clin Sci (Lond) 2017;131:2241-56.  Back to cited text no. 14
    
15.
Lewis AM, Varghese S, Xu H, Alexander HR. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med 2006;4:48. [doi: 10.1186/1479-5876-4-48].  Back to cited text no. 15
    
16.
Ray AL, Berggren KL, Restrepo Cruz S, Gan GN, Beswick EJ. Inhibition of MK2 suppresses IL-1β, IL-6, and TNF –α-dependent colorectal cancer growth. Int J Cancer 2018;142:1702-11.  Back to cited text no. 16
    
17.
Hai Ping P, Feng Bo T, Li L, Nan Hui Y, Hong Z. IL-1β/NF-κB promotes colorectal cancer cell growth through miR-181a/PTEN axis. Arch Biochem Biophys 2016;604:20-6.  Back to cited text no. 17
    
18.
Wang Y, Xu H, Jiao H, Wang S, XIo Z, Zhao Y, et al. STX2 promotes colorectal cancer metastasis through a positive feedback loop that activates the NF-κB pathway. Cell Death Dis 2018;9:664.  Back to cited text no. 18
    
19.
Sheng YH, He Y, Hasnain SZ, Wang R, Tong H, Clarke DT, et al. MUC13 protects colorectal cancer cells from activating the NF-κB pathway and is a potential therapeutic target. Oncogene 2017;36:700-13.  Back to cited text no. 19
    
20.
Soleimani A, Rahmani F, Ferns GA, Ryzhikov M, Avan A, Hassanian SM. Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer. Gene 2020;726:144132.  Back to cited text no. 20
    
21.
Kai H, Kitadai Y, Kodama M, Cho S, Kuroda T, Ito M, et al. Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of human gastric carcinoma. Anticancer Res 2005;25:709-13.  Back to cited text no. 21
    
22.
Vidal-Vanaclocha F, Fantuzzi G, Mendoza L, Fuentes AM, Anasagasti MJ, Martin J, et al. IL-18 regulates IL-1-beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proc Natl Acad Sci U S A 2000;97:734-9.  Back to cited text no. 22
    
23.
Gui G, Yuan A, Sun ZL, Zheng W, Pang ZG. IL-1β/IL-6 network in the tumor microenvironment of human colorectal cancer. Pathol Res Pract 2018;214:986-92.  Back to cited text no. 23
    
24.
Epstein J, Docena G, MacDonald TT, Sanderson IR. Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1β and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr 2010;103:824-32.  Back to cited text no. 24
    
25.
Das L, Vinayak M. Curcumin attenuates carcinogenesis by downregulating proinflammatory cytokine interleukin-1 (IL-1α and IL-1β) via modulation of AP-1 and NF-IL6 in lymphoma bearing mice. Int Immunopharmacol 2014;20:141-7.  Back to cited text no. 25
    
26.
Jeon M, Han J, Nam SJ, Lee JE, Kim S. Elevated IL-1β expression induces invasiveness of triple negative breast cancer cells and is suppressed by zerumbone. Chem Biol Interact 2016;258:126-33.  Back to cited text no. 26
    
27.
Li Y, Wang L, Pappan L, Beckley AG, Shi J. IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer 2012;11:87.  Back to cited text no. 27
    
28.
Ismail NI, Othman I, Abas F, Lajis NH, Naidu R. Mechanism of apoptosis induced by curcumin in colorectal cancer. Int J Mol Sci 2019;20:2454.  Back to cited text no. 28
    
29.
Mirzaei H, Masoudifar A, Sahebkar A, Zare N, Sadri Nahand J, Rashidi B, et al. MicroRNA: A novel target of curcumin in cancer therapy. J Cell Physiol 2018;233:3004-15.  Back to cited text no. 29
    
30.
Wang Y, Tang Q, Duan P, Yang L. Curcumin as a therapeutic agent for blocking NF-κB activation in ulcerative colitis. Immunopharmacol Immunotoxicol 2018;40:476-82.  Back to cited text no. 30
    
31.
Qiang Z, Meng L, Yi C, Yu L, Chen W, Sha W. Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells. J Int Med Res 2019;47:1288-97.  Back to cited text no. 31
    
32.
Qi L, Jiang J, Zhang J, Zhang L, Wang T. Curcumin protects human trophoblast HTR8/SVneo cells from H2O2-induced oxidative stress by activating Nrf2 pathway. Antioxidants (Basel) 2020;9:E121.  Back to cited text no. 32
    
33.
Zhang H, Sun SC. NF-κB in inflammation and renal disease. Cell Biosci 2015;5:63.  Back to cited text no. 33
    
34.
Banoth B, Chatterjee B, Vijayaragavan B, Prasad MV, Roy P, Basak S. Stimulus-selective crosstalk via the NF-κB signaling system reinforces innate immune response to alleviate gut infection. Elife 2015;23:4.  Back to cited text no. 34
    
35.
Park MH, Hong JT. Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cells 2016;5:E15.  Back to cited text no. 35
    
36.
Jiang C, Zhu Y, Zhou Z, Gumin J, Bengtsson L, Wu W, et al. TMEM43/LUMA is a key signaling component mediating EGFR-induced NF-κB activation and tumor progression. Oncogene 2017;36:2813-23.  Back to cited text no. 36
    
37.
Wang Y, Bao X, Zhao A, Zhang J, Zhang MY, Zhang Q, et al. Raddeanin a inhibits growth and induces apoptosis in human colorectal cancer through downregulating the Wnt/β-catenin and NF-κB signaling pathway. Life Sci 2018;207:532-49.  Back to cited text no. 37
    
38.
Lee J, Park JR, Lee H, Jang S, Ryu SM, Kim H, et al. L-carnosine induces apoptosis/cell cycle arrest via suppression of NF-κB/STAT1 pathway in HCT116 colorectal cancer cells. In Vitro Cell Dev Biol Anim 2018;54:505-12.  Back to cited text no. 38
    
39.
Ghasemi F, Shafiee M, Banikazemi Z, Pourhanifeh MH, Khanbabaei H, Shamshirian A, et al. Curcumin inhibits NF-κB and Wnt-β-catenin pathways in cervical cancer cells. Pathol Res Pract 2019;215:152556.  Back to cited text no. 39
    
40.
Tian F, Zhang C, Tian W, Jiang Y, Zhang X. Comparison of the effect of p65 siRNA and curcumin in promoting apoptosis in esophageal squamous cell carcinoma cells and in nude mice. Oncol Rep 2012;28:232-40.  Back to cited text no. 40
    
41.
Hesari A, Azizian M, Sheikhi A, Nesaei A, Sanaei S, Mahinparvar N, et al. Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status. Int J Cancer 2019;144:1215-26.  Back to cited text no. 41
    
42.
Bimonte S, Barbieri A, Palma G, Rea D, Luciano A, D'Aiuto M, et al. Dissecting the role of curcumin in tumour growth and angiogenesis in mouse model of human breast cancer. Biomed Res Int 2015;2015:878134.  Back to cited text no. 42
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures

 Article Access Statistics
    Viewed97    
    Printed4    
    Emailed0    
    PDF Downloaded21    
    Comments [Add]    

Recommend this journal