Abstract
Background
TMS (2,3′,4,5′-tetramethoxystilbene), a stilbene analog derived from rhapontigenin, was previously demonstrated to induce apoptosis in hormone-resistant breast cancer cells. Therefore, this study investigated the anticancer effect of a new stilbene analog, HTMS ((E)-2-hydroxy-3′,4,5′-trimethoxystilbene), and its mechanism in various breast cancer cell lines.
Materials and methods
The effect of HTMS on cell proliferation of MDA-MB-231, MCF-7, and LTED cells was evaluated using MTT assays. Cell apoptosis was detected by FITC-annexin V staining and flow cytometry analysis, changes in mitochondrial potential were determined by fluorescence microscopy using TMRE staining, and the expression of cleaved PARP and release of cytochrome c were assessed by Western blot analysis.
Results
HTMS significantly decreased the cell viability of various types of breast cancer cells in a dose- and time-dependent manner, characterized by G2/M arrest of the cell cycle and the induction of apoptosis. In particular, HTMS disturbed the mitochondrial membrane potential, causing a release of cytochrome c during apoptosis. Furthermore, HTMS was superior to TMS in inhibiting cancer cell growth in a pilot comparison study.
Conclusion
HTMS is an effective apoptotic agent for breast cancer cells, making it a candidate therapeutic agent for the treatment of breast cancer.
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Abbreviations
- DMSO:
-
Dimethylsulfoxide
- HTMS:
-
(E)-2-Hydroxy-3′,4,5′-trimethoxystilbene
- LTED breast cancer:
-
Long-term estradiol-deprived breast cancer
- MTT:
-
3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide
- PI:
-
Propidium iodide
- Rhapontigenin:
-
3,5,3′-Trihydroxy-4′-methoxy-trans-stilbene
- TMS:
-
2,3′,4,5′-Tetramethoxystilbene
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Acknowledgments
This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean Government (MEST) (No. 2009-0091573).
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Y. S. Chae and H. J. Jung contributed equally to this article as the first authors.
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Chae, Y.S., Kim, J.G., Jung, H.J. et al. Anticancer effect of (E)-2-hydroxy-3′,4,5′-trimethoxystilbene on breast cancer cells by mitochondrial depolarization. Cancer Chemother Pharmacol 68, 349–358 (2011). https://doi.org/10.1007/s00280-010-1464-0
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DOI: https://doi.org/10.1007/s00280-010-1464-0