Role of Organic Cation Transporter 2 in Autophagy Induced by Platinum Derivatives

Abstract

The human organic cation transporter 2 (hOCT2) mediates renal and neuronal cellular cisplatin and oxaliplatin uptake, and therefore plays a significant role in the development of side effects associated with these chemotherapeutic drugs. Autophagy is induced by cisplatin and oxaliplatin treatment and is believed to promote cell survival under stressful conditions. We examined in vitro the role of hOCT2 on autophagy induced by cisplatin and oxaliplatin. We also explored the effect of autophagy on toxicities of these platinum derivatives. Our results indicate that autophagy, measured as LC3 II accumulation and reduction in p62 expression level, is induced in response to cisplatin and oxaliplatin in HEK293-hOCT2 but not in wild-type HEK293 cells. Furthermore, inhibition of autophagy is associated with higher toxicity of platinum derivatives, and starvation was found to offer protection against cisplatin-associated toxicity. In conclusion, activation of autophagy could be a potential strategy to protect against unwanted toxicities induced by treatment with platinum derivatives.

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“…Platinum-based drugs, like cisplatin and oxaliplatin, are largely explored in the organ cation transporter arena, including SLC22A1 and SLC22A2 (20). Organic anion transporters (OAT or SLC22A) play an extremely vital role in renal dysfunction and are widely recognized as drug transporters.…”

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“…Autophagy seems to be a mechanism by which cells can protect themselves against damage induced by pharmacological treatment. In the paper “Role of Organic Cation Transporter 2 in Autophagy Induced by Platinum Derivatives”, Ahmed-Eltayeb et al [ 9 ] investigated the role of hOCT2 on autophagy induced by Cisplatin and Oxaliplatin. They also explored the effect of autophagy activation by starvation on the toxicities of these Platinum derivatives.…”