The dose dependent in vitro responses of MCF-7 and MDA-MB-231 cell lines to extracts of Vatica diospyroides symington type SS fruit include effects on mode of cell death

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Abstract
Pharmacognosy Magazine,2015,11,42s,s148-s155.
Published:May 2015
Type:Original Article
Authors:
Author(s) affiliations:

Theera Srisawat1, Yaowapa Sukpondma2, Potchanapond Graidist3, Siriphon Chimplee4, Kanyanatt Kanokwiroon3
1 Department of Agricultural Science and Technology, Faculty of Science and Industrial Technology, Prince of Songkla University, Suratthani Campus, Suratthani 84000, Thailand
2 Department of Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
3 The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Hat Yai, Songkhla 90110; Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
4 Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand

Abstract:

Background: Vatica diospyroides type LS is a known source of valuable compounds for cancer treatment, however, in contrast little is known about therapeutic efficacy of type SS. Objective: This study focused on in vitro cytotoxicity of these fruit extracts, and the cell death mode they induce in breast cancer cells. Materials and Methods: Acetone extracts of fruit were tested for cytotoxicity against MCF-7 and MDA-MB-231 cell lines. The apoptosis and necrosis of these cells were quantified by fluorescence activated cell sorter (FACS) and western blot analyses. Results: After 72 h of treatment, the 50% growth inhibition concentrations (IC 50 ) levels were 16.21 ± 0.13 µg/mL against MCF-7 and 30.0 ± 4.30 µg/mL against MDA-MB-231, indicating high and moderate cytotoxicity, respectively. From the FACS results, we estimate that the cotyledon extract at half IC 50 produced 11.7% dead MCF-7 cells via apoptosis, whereas another concentrations both apoptosis and necrosis modes co-existed in a dose-dependent manner. In MDA-MB-231 cell line, only the apoptosis was induced by the pericarp extract in a dose-dependent manner. With the extracts at half IC 50 concentration, in both cells, the expression of p21 decreased while that of Bax increased within 12-48 h of dosing, confirming apoptosis induced by time-dependent responses. Apoptosis dependent on p53 was found in MCF-7, whereas the mutant p53 of MDA-MB-231 cells was expressed. Conclusion: The results indicate that fruit extracts of V. diospyroides have cytotoxic effects against MCF-7 and MDA-MB-231 cells via apoptosis pathway in a dose-dependent manner. This suggests that the extracts could provide active ingredients for the development, targeting breast cancer therapy.

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