8P - The impact of rotenone-modulated oxidative stress on the survival of human breast cancer stem cells (CD24-/CD44+)

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Basic Science
Breast Cancer
Presenter Septelia Wanandi
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors S.I. Wanandi1, R.A. Syahrani2, S.W.A. Jusman1
  • 1Biochemistry And Molecular Biology, Faculty of Medicine, Universitas Indonesia, 10430 - Jakarta/ID
  • 2Master Program In Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, 10430 - Jakarta/ID

Abstract

Background

Cancer stem cells (CSCs) have been proven to be tumorigenic and may be responsible for the resistance to chemo-radiation therapy, disease recurrence and metastasis. Chemo-radiation therapy modulates oxidative stress in cancer cells, leading to cellular adaption response including modulation of cell survival and antioxidant defense mechanisms. However, the redox status alteration of breast CSCs is not yet clearly understood. The aim of this study was to elaborate the impact of rotenone-modulated oxidative stress on the survival of human breast CSCs (CD24-/CD44+) which might be beneficial to understand the underlying mechanism of chemo-radiation therapy resistance.

Methods

Human breast CSCs (CD24-/CD44+) and non-CSCs (CD24-/CD44-) were treated with rotenone and DMSO (vehicle) for 6 hours, respectively. The effects of rotenone on oxidative stress were assessed by analysing intracellular reactive oxygen species (ROS) level using dihydroethidium assay, as well as mRNA expression and specific activity of MnSOD antioxidant. Finally, cell survival was determined using MTS assay, as well as through analysis of survivin mRNA expression.

Results

Our results showed that rotenone could not modulate the superoxide level of human breast CSCs (CD24-/CD44+), in contrast to that of non-CSCs (CD24-/CD44-). Albeit MnSOD synthesis in human breast CSCs has been excessively enhanced following rotenone treatment, the enzyme activity was still lower than in non-CSCs. Importantly, the cell viability of CSCs was higher than that of non-CSCs, which related to the increase of survivin.

Conclusions

We conclude that human breast CSCs (CD24-/CD44+) could survive better than their counterpart non-CSCs (CD24-/CD44-) when treated with rotenone. This impact might be associated with the increase of antioxidant MnSOD expression and survivin mRNA expression.

Clinical trial identification

Legal entity responsible for the study

Faculty of Medicine, Universitas Indonesia

Funding

None

Disclosure

All authors have declared no conflicts of interest.