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The mediation of intracellular Ca 2+ by resveratrol
Author(s) -
Mecham Jeffrey C
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.690.24
Subject(s) - downregulation and upregulation , resveratrol , intracellular , bapta , microbiology and biotechnology , extracellular , cancer cell , calcium in biology , cytosol , apoptosis , chemistry , cancer research , calcium , programmed cell death , biology , cancer , biochemistry , genetics , organic chemistry , gene , enzyme
Breast cancer constitutes a major problem among American Women. Current chemotherapeutic options for breast cancer are limited by their toxicity to normal tissue . The naturally occurring polyphenol resveratrol has been shown to induce tumor‐cell specific apoptosis in many cancer‐cell lines, including breast cancer cells. Treatment of MDA‐MB‐231 with resveratrol leads to an upregulation of tumor suppressor protein p53, a key protein in the apoptotic pathway. Using the intracellular‐calcium chelator BAPTA, we show inhibition of the upregulation of p53 upon treatment of resveratrol, indicating that Ca 2+ regulation in the cytosol plays a crucial role in the mechanism of resveratrol in mediating cell death. Plasma Membrane Calcium ATP‐ase (PMCA) extrudes calcium from the cytosol into the extracellular space. Because of the characteristic upregulation of PMCA in MDA‐MB‐231 cells and other cancer cell lines as compared to normal cells, it is a novel target for chemotherapeutic treatment. Using the known PMCA inhibitor LaCl 3 , we show that resveratrol inhibits PMCA, leading to upregulation of p53 . We further determine the role of the hydroxyl groups of resveratrol in p53 upregulation