Suppression of rotenone-treated human breast cancer stem cell survival using survivin inhibitor YM155 is associated to oxidative stress modulation

Resda A. Syahrani, Elvira Yunita, Septelia I. Wanandi

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Despite recent progress in molecular-targeted therapies, breast cancer remains the primary leading cause of cancer related death among women worldwide. Breast cancer stem cells (BCSCs) are believed to be responsible for therapy resistance and cancer recurrence. We recently demonstrated that human BCSCs (CD24-/CD44+) could survive better than their counterpart non-BCSCs (CD24-/CD44-) when treated with rotenone, possibly due to lower levels of reactive oxygen species (ROS) production, high expression of antioxidant manganese superoxide dismutase (MnSOD), and anti-apoptotic survivin. The aim of this study was to verify the role of survivin on human BCSCs survival under oxidative stress modulation by suppressing its expression using YM155, a survivin inhibitor. Methods: Human BCSCs (ALDH+ cells) were treated with YM155 for 24 h prior to treatment with rotenone for a further 6 h. We determined intracellular superoxide levels were determined using dihydroethidium assay, survivin and MnSOD expression using qRT-PCR, survivin protein level using ELISA, as well as cell viability using trypan blue exclusion and acridine orange/ethidium bromide apoptosis assay. Results: Suppression of survivin expression using YM155 could reduce the survival of rotenone-treated BCSCs, which may be associated with oxidative stress modulation, as shown by increased ROS levels and decreased MnSOD expression. We confirm that survivin is responsible for maintaining BCSCs survival under oxidative stress modulation. Furthermore, YM155 could modulate oxidative stress in BCSCs by reducing MnSOD expression and increasing ROS levels. Conclusion: YM155 treatment could be used to overcome BCSCs resistance to oxidative stress-based anticancer therapies.

Original languageEnglish
Pages (from-to)2631-2637
Number of pages7
JournalAsian Pacific Journal of Cancer Prevention
Volume21
Issue number9
DOIs
Publication statusPublished - 1 Sep 2020

Keywords

  • Breast cancer stem cells
  • Oxidative stress
  • Survivin
  • YM155

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