Paclitaxel induces apoptosis in breast cancer cells through different calcium-regulating mechanisms depending on external calcium conditions

Zhi Pan, Andrew Avila, Lauren Gollahon

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an "Enhanced Calcium Efflux" mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel's stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis.

Original languageEnglish
Pages (from-to)2672-2694
Number of pages23
JournalInternational journal of molecular sciences
Volume15
Issue number2
DOIs
StatePublished - Feb 17 2014

Keywords

  • Apoptosis
  • Breast cancer
  • Endoplasmic reticulum
  • External calcium
  • Paclitaxel

Fingerprint Dive into the research topics of 'Paclitaxel induces apoptosis in breast cancer cells through different calcium-regulating mechanisms depending on external calcium conditions'. Together they form a unique fingerprint.

  • Cite this