ERK1/2 activation is required for resveratrol-induced apoptosis in MDA-MB-231 cells

  • Authors:
    • Thanh-Hung Nguyen
    • Fatimah B. Mustafa
    • Shazib Pervaiz
    • Florence S.P. Ng
    • Lina H.K. Lim
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.81
  • Pages: 81-92
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Abstract

Resveratrol (RSVL), a phytoalexin found in abundance in grapes and other grape-related products, has been shown to be antiproliferative and protective against various types of cancers, including breast cancer. However, the precise underlying mechanisms are not well understood. In this study, we show that treatment with RSVL induces growth inhibition and apoptosis in a highly invasive and metastatic breast cancer cell line MDA-MB-231. Cleavage of caspase-3 and PARP and fragmentation of DNA were observed following exposure to RSVL. Co-treatment with pan-caspase inhibitor completely prevents cell death induced by RSVL. We found that RSVL-induced apoptosis correlates with sustained activation of ERK1/2 and suppression of Bcl-2 expression. Inhibition of ERK1/2 activation by its specific inhibitor or small interfering RNA reverses the effect of RSVL on Bcl-2 suppression and inhibits apoptosis, while overexpression of MEK1, which is directly upstream of both ERK1 and ERK2, enhances apoptosis induced by RSVL. Moreover, ERK1/2 was found to act upstream of caspase-3 to induce apoptosis, while it was not directly involved in caspase-3 cleavage. The other closely related MAPK members, p38 and JNK are not involved in apoptosis induced by RSVL in MDA-MB-231 cells. These results suggest that activation of ERK1/2 is required for RSVL-induced apoptosis in MDA-MB-231 cells.

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July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Nguyen T, Mustafa FB, Pervaiz S, Ng FS and Lim LH: ERK1/2 activation is required for resveratrol-induced apoptosis in MDA-MB-231 cells. Int J Oncol 33: 81-92, 2008.
APA
Nguyen, T., Mustafa, F.B., Pervaiz, S., Ng, F.S., & Lim, L.H. (2008). ERK1/2 activation is required for resveratrol-induced apoptosis in MDA-MB-231 cells. International Journal of Oncology, 33, 81-92. https://doi.org/10.3892/ijo.33.1.81
MLA
Nguyen, T., Mustafa, F. B., Pervaiz, S., Ng, F. S., Lim, L. H."ERK1/2 activation is required for resveratrol-induced apoptosis in MDA-MB-231 cells". International Journal of Oncology 33.1 (2008): 81-92.
Chicago
Nguyen, T., Mustafa, F. B., Pervaiz, S., Ng, F. S., Lim, L. H."ERK1/2 activation is required for resveratrol-induced apoptosis in MDA-MB-231 cells". International Journal of Oncology 33, no. 1 (2008): 81-92. https://doi.org/10.3892/ijo.33.1.81