Synergic prooxidant, apoptotic and TRPV1 channel activator effects of alpha-lipoic acid and cisplatin in MCF-7 breast cancer cells

Abstract

Background: Resistance to cisplatin (Cisp) in the treatment of breast cancer is a major obstacle. Alpha-lipoic acid (ALA) has both antioxidant and oxidant properties. ALA has been used on stimulation mechanisms of apoptosis and oxidative stress in the treatment of cancer with a combination of chemotherapeutic agents, although its role on molecular mechanisms in the cancer cells has not been clarified yet. The aim of this study was to evaluate if a combination therapy of ALA with Cisp can alter the effect of this chemotherapy drug in the MCF-7 breast cancer cells.

Materials: The MCF-7 cells were divided into four treatment groups as control, Cisp (0.025 mM), ALA (0.05 mM), and Cisp + ALA.

Results: Apoptosis, mitochondrial membrane depolarization, reactive oxygen species (ROS) production, lipid peroxidation, PARP1, caspase 3 and 9 expression levels are increased through activating TRPV1 in the cells by the Cisp and ALA treatments, although cell viability, reduced glutathione and glutathione peroxidase (GPx) values were decreased by the treatments. The Cisp and ALA-induced increase of intracellular free Ca²⁺ concentration was decreased with the TRPV1 blocker, capsazepine.

Conclusions: Apoptosis and oxidant effects of Cisp were increased by activation of TRPV1 channels, but its action on the values was further increased by the ALA treatment. Combination therapy of ALA and Cisp could be used as an effective strategy in the treatment of breast cancer.

Keywords:

• α-Lipoic acid
• prooxidant
• apoptosis
• breast cancer
• cisplatin
• TRPV1 channel

Acknowledgements

Mustafa Nazıroğlu formulated the present hypothesis and was responsible for writing the report. Gökhan Nur and Haci Ahmet Deveci were responsible for analysis of the data. The authors wish to thanks Dr. İshak Suat Övey (Neuroscience Research Center, SDU, Isparta, Turkey) for helping the western blot analyses. Abstract of the study will be presented in 2nd International Brain Research School, to be held in Isparta (Turkey) between 6 and 12 November 2017 (http://www.cmos.org.tr/brs2017/en/).

Disclosure statement

No potential conflict of interest was reported by the authors.