In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells

  • Authors:
    • Emma C. Stuart
    • Reagan M. Jarvis
    • Rhonda J. Rosengren
  • View Affiliations

  • Published online on: September 1, 2010     https://doi.org/10.3892/or_00000921
  • Pages: 779-785
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Abstract

The anticancer effects elicited by epigallocatechin gallate (EGCG) are well established in various models of cancer, while raloxifene is as an established selective estrogen receptor modulator (SERM), which is not yet clinically utilized for the treatment of breast cancer. Previous study from this laboratory has demonstrated that the combination of EGCG (25 µM) and raloxifene (4 µM) elicits a strong cytotoxic response in MDA-MB-231 human breast cancer cells, which lack the estrogen receptor (ER) and erbB-2/ Her-2 receptor. This study was therefore designed to probe the mechanism underlying this cytotoxic response, with an emphasis on determining how the combination treatment influenced the total expression and phosphorylation of key signaling proteins. Specifically, following 12 and 18 h of the combination treatment, we observed significant decreases in the phosphorylation of the epidermal growth factor receptor (EGFR), AKT, mammalian target of rapamycin (mTOR) and S-6-kinase (S6K), and significant increases in the phosphorylation of stress activated protein kinases (SAPKs). Furthermore, these changes were associated with a reduction in the nuclear localization of p65, a major subunit of NF-κB. These results demonstrate that the combination of EGCG and raloxifene effectively reduced the mitogenic and survival signaling in MDA-MB-231 cells. Thus, this combination warrants further experimentation as a potential treatment for ER-negative breast cancer.

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September 2010
Volume 24 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Stuart EC, Jarvis RM and Rosengren RJ: In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells . Oncol Rep 24: 779-785, 2010.
APA
Stuart, E.C., Jarvis, R.M., & Rosengren, R.J. (2010). In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells . Oncology Reports, 24, 779-785. https://doi.org/10.3892/or_00000921
MLA
Stuart, E. C., Jarvis, R. M., Rosengren, R. J."In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells ". Oncology Reports 24.3 (2010): 779-785.
Chicago
Stuart, E. C., Jarvis, R. M., Rosengren, R. J."In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells ". Oncology Reports 24, no. 3 (2010): 779-785. https://doi.org/10.3892/or_00000921