Mitochondrial characteristics contribute to proliferation and migration potency of MDA-MB-231 cancer cells and their response to cisplatin treatment

Abstract

Aim: Despite recent advances in therapeutic strategies, cancer is still a leading cause of mortality worldwide. Mitochondrial dysfunction is implicated in cancer initiation and metastasis, and even in chemo- and radio-resistance. However, the precise role of mitochondria in cancer is crosstalk and controversial. This study is trying to find out the effect of transferring normal mitochondria into the highly aggressive and proliferative MDA-MB-231 cancer cells, and to evaluate the effect of the transfer with/without a combination therapy with cisplatin. Materials and methods: Normal mitochondria were isolated from human umbilical cord derived-mesenchymal stem cells. The mitochondria were transferred into the MDA-MB-231 cells, and also into cells with mitochondrial dysfunction induced by rhodamine red 6 (R6G). Cell proliferation and sensitivity of the cells to cisplatin were measured by cell counting after the mitochondria transfer. Also, apoptosis was evaluated by DAPI staining and in situ cell death detection (TdT-mediated dUTP nickend labeling; TUNEL) methods. Migration capability of the cells was studied by transwell assay. Key findings: Transfer of normal mitochondria into MDA-MB-231 cells increased cell proliferation. However, the transfer of mitochondria enhanced cisplatin-induced apoptosis in MDA-MB-231 cells in which mitochondria were already disrupted. Introduction of normal cell-derived mitochondria into the MDA-MB-231 cells increased their invasive, but decreased the migration potency of the cells in the group with mitochondrial dysfunction (MDA + RG6 + Cisplatin). Conclusion: The introduction of healthy mitochondria to highly aggressive and proliferative cells would be considered as a new therapeutic modality for some types of cancer.