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Anticancer effect of (E)-2-hydroxy-3′,4,5′-trimethoxystilbene on breast cancer cells by mitochondrial depolarization

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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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Authors and Affiliations

  1. Department of Medical Oncology, Kyungpook National University Hospital, Daegu, South Korea

    Yee Soo Chae & Jong Gwang Kim

  2. Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, South Korea

    Hyun Jun Jung & Hoyong Park

  3. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, South Korea

    Hyun Jun Jung

  4. Department of Plastic surgery, Kyungpook National University Hospital, Daegu, South Korea

    Jung Dug Yang

  5. Department of Surgery, Kyungpook National University Hospital, Samduck-2 Ga, Jung-gu, Daegu, 700-721, South Korea

    Jin Hyang Jung & Hoyong Park

  6. Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, US

    Sarah E. Aiyar

  7. College of Pharmacy, Seoul National University, Seoul, South Korea

    Sanghee Kim

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  1. Yee Soo Chae
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  2. Jong Gwang Kim
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Corresponding author

Correspondence to Hoyong Park.

Additional information

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

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