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Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the

Xiu-Fang Wang1, Paul K Witting, Brian A Salvatore

  • 1Apoptosis Research Group, School of Health Science, Griffith University, Southport, Qld, Australia.

Biochemical and Biophysical Research Communications
|December 8, 2004
PubMed

Insights

Alpha-tocopheryl succinate (alpha-TOS), a vitamin E analog, effectively induces cancer cell death (apoptosis) in breast cancer cells, regardless of HER2/erbB2 protein levels. This finding is significant for developing new cancer treatments.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Vitamin E (VE) analogs, like alpha-tocopheryl succinate (alpha-TOS), exhibit anti-neoplastic properties.
  • HER2/erbB2 overexpression is common in breast cancers, contributing to treatment resistance.

Purpose of the Study:

  • To investigate the efficacy of alpha-TOS and novel VE analogs in inducing apoptosis in breast cancer cells with varying HER2/erbB2 expression levels.
  • To elucidate the mechanisms underlying VE analog-induced apoptosis in breast cancer cells.

Main Methods:

  • Treatment of breast cancer cells (erbB2-low and -high) with alpha-TOS and VE analogs.
  • Assessment of apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (DeltaPsi(m)).
  • Use of superoxide dismutase, mitochondrially targeted coenzyme Q, and rho(0) cells to confirm mechanisms.

Main Results:

  • Alpha-TOS and VE analogs induced apoptosis comparably in both erbB2-low and -high cells.
  • Apoptosis was preceded by ROS generation and mitochondrial destabilization (DeltaPsi(m) dissipation).
  • Mitochondrial dependence and radical generation were confirmed as critical for VE analog-mediated apoptosis.

Conclusions:

  • Alpha-tocopheryl succinate effectively induces apoptosis in breast cancer cells irrespective of HER2/erbB2 expression.
  • The findings suggest alpha-TOS as a potential therapeutic agent for breast cancers, including those resistant to conventional treatments due to HER2/erbB2 overexpression.

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