title: Paclitaxel attenuates Bcl-2 resistance to apoptosis in breast cancer cells through an endoplasmic reticulum-mediated calcium release in a dosage dependent manner.
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.
authors: Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409-3131, United States. zhi_pan@yahoo.com
authors: Zhi
authors: Z
authors: Pan
authors: Lauren
authors: L
authors: Gollahon
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D017239:Paclitaxel; D002118:Calcium