Gallic Acid Enhances Cisplatin-induced Death of Human Laryngeal Cancer Cells by Activating the TRPM2 Channel

Abstract

Cisplatin (CIS) is widely used in the treatment of laryngeal cancer, one of the most common and lethal cancers. However, it is not a satisfactory chemotherapeutic agent. Therefore, there is a need to identify new agents, such as gallic acid (GAL), that can exert a synergistic effect to elucidate the pathophysiological mechanisms of the chemotherapeutic effects of CIS and to increase the effectiveness of treatment by preventing drug resistance. For this purpose, we investigated the stimulatory role of GAL on CIS-induced human laryngeal cancer (Hep-2) cell death via TRPM2 channel activation. For the study, four groups were formed from human laryngeal cancer (Hep-2) cells as Control, GAL (1OO mu M), CIS (25 mu M), and GAL + CIS. In the analyses made, cell viability, glutathione (GSH) and glutathione peroxidase (GSH-Px) enzyme activity, lipid peroxidation (LPx) levels, inflammation markers I-1 beta, IL-6, and TNF-alpha, Total Oxidant/Antioxidant (TOS and TAS) status, reactive oxygen species (ROS), caspase (Cas-3-9) activity, Transient Receptor Potential Melastatin 2 (TRPM2), and Poly Adp Ribose Polymerase-1, (PARP-1) levels in the cells were determined. CIS treatment caused laryngeal cancer cell cytotoxic and increased Cas-3-9, ROS, IL-1 beta, TNF-alpha, IL-6, TOS, LPx, TRPM2, and PARP-1 levels while decreasing cell viability, GSH-Px, GSH, and TAS levels. The combination of GAL and CIS treatment made the treatment even more effective. In conclusion, the increase in ROS and cell death levels mediated by TRPM2 activation in CIS Hep-2 cells was further enhanced by GAL treatment. Thus, CIS chemotherapy in Hep-2 cells may be enhanced by the synergistic effect of the GAL combination, and drug resistance may be reduced.