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Al-Qatati A, Aliwaini S. Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells. Oncol Lett. 2017;14(6):7993-7999doi: 10.3892/ol.2017.7189.
Al-Qatati, A., & Aliwaini, S. (2017). Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells. Oncology letters, 14(6), 7993-7999. https://doi.org/10.3892/ol.2017.7189
Al-Qatati, Abeer, and Aliwaini, Saeb. "Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells." Oncology letters vol. 14,6 (2017): 7993-7999. doi: https://doi.org/10.3892/ol.2017.7189
Al-Qatati A, Aliwaini S. Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells. Oncol Lett. 2017 Dec;14(6):7993-7999. doi: 10.3892/ol.2017.7189. Epub 2017 Oct 16. PMID: 29344241; PMCID: PMC5755017.
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Oncol Lett. 2017 Dec;14(6):7993-7999. doi: 10.3892/ol.2017.7189. Epub 2017 Oct 16.

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells.

Oncology letters

Abeer Al-Qatati, Saeb Aliwaini

Affiliations

  1. Faculty of Applied Medical Sciences, Al-Azhar University, Gaza 1277, Palestine.
  2. Department of Biological Sciences and Biotechnology, Faculty of Sciences, Islamic University of Gaza, Gaza 108, Palestine.

PMID: 29344241 PMCID: PMC5755017 DOI: 10.3892/ol.2017.7189

Abstract

Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma.

Keywords: apoptosis; autophagy; dacarbazine; melanoma; pitavastatin

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