Gökhan Nur

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.

The effect of caffeic acid phenethyl ester (CAPE) on hepatic histopathology and oxidative stress in rats treated with malathion

Malathion is a broad-spectrum organophosphate insecticide used in the agricultural industry. Our study aimed to investigate the protective effects of caffeic acid phenethyl ester (CAPE) against malathion by examining histopathological and biochemical parameters. Forty Sprague-Dawley male rats were used in this study. Groups formed; group I (control), only 5 ml kg-1 oral corn oil; group II (malathion), 40 mg kg-1 malathion by gavage; group III (malathion+CAPE), intraperitoneal (i.p.) CAPE (10 μmol kg-1) followed by intragastric malathion (40 mg kg-1) after 1 hour; group IV (CAPE), intraperitoneal CAPE (10 μmol kg-1). At the end of the administrations, rats were anesthetised with ketamine/xylazine intraperitoneally and euthanasia was performed with cervical dislocation. Their intracardiac blood was drawn under anaesthesia, and after the euthanasia, their liver tissues were removed for histopathological analysis. In group II that was treated with malathion, cell infiltrations around the central and portal vein, degeneration and focal necrosis areas in the liver were detected. Although the histopathological findings observed in the malathion group were also encountered in group III (malathion+CAPE), lesions were less severe. In the malathion group II, total oxidant status (TOS) and total sialic acid (TSA) levels in plasma increased compared with the control group, while total antioxidant status (TAS) decreased compared with the control group. In the Malathion+CAPE group III, it was observed that biochemical parameters were closer to the control group. In malathion-treated rats, it was determined that CAPE reduced the degeneration in the liver and it could have a protective effect by partially correcting oxidative stress parameters. It was concluded based on our findings that malathion, which is an organophosphate compound, makes toxic effects in the liver, but that CAPE has a protective potential because it partially reduces the severity and frequency of histopathological lesions and it brings biochemical values closer to normal.