Paclitaxel attenuates Bcl-2 resistance to apoptosis in breast cancer cells through an endoplasmic reticulum-mediated calcium release in a dosage dependent manner

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Abstract

To address the controversy regarding efficacy of paclitaxel in the presence of the anti-apoptotic protein Bcl-2, we investigated calcium stored in the endoplasmic reticulum as a potential factor. Our results showed that the ER calcium store is a common target for both paclitaxel and Bcl-2 protein. Paclitaxel directly associates with the endoplasmic reticulum to stimulate the release of calcium into the cytosol, contributing to the induction of apoptosis. However, Bcl-2 expression suppresses the cell's pro-apoptotic response of endoplasmic reticulum calcium release, thus inhibiting susceptibility of cancer cells to undergo apoptosis. Depending upon dosage, a paclitaxel-induced stimulatory effect can overcome the Bcl-2-mediated inhibitory effect on endoplasmic reticulum calcium release, thus attenuating the resistance of Bcl-2 to apoptosis. Our finding is the first to demonstrate that endoplasmic reticulum calcium plays a key role in the efficacy of paclitaxel in the presence of Bcl-2, thus providing insight into the complex but crucial paclitaxel-calcium-Bcl-2 relationship, which may impact breast cancer treatment.

Original languageEnglish
Pages (from-to)431-437
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume432
Issue number3
DOIs
StatePublished - Mar 15 2013

Keywords

  • Apoptosis
  • Bcl-2
  • Breast cancer
  • Calcium
  • Endoplasmic reticulum
  • Paclitaxel

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