Effect of A Synthetic Platinum-Based Complex on AutophagyInduction in Sertoli TM۴ Cells

Background: Platinum-based chemotherapy that are widelyused in clinical, have major limitations and various side effects.Gonadotoxicity and s terility are the mos t common complicationsfor cancer survivors, which is drug-specific and doserelated.We aimed to inves tigate the cytotoxicity effect of newsynthesized Pt(II)-phosphane complexes containing heterocyclicthionate ligands (PCTL) on mice TM۴ Sertoli cells withparticular emphasis on the role of autophagy.Materials and Methods: MTT assay was performed to evaluatethe IC۵۰ of PCTL and to analyze the TM۴ cells' viability.Cells morphology was evaluated via invert microscope, and nucleiswelling or autophagic vacuoles formation were assessedby DAPI and MDC s taining. Finally, the expression of Atg۵,Beclin۱, p۶۲, BAX and BCL۲ were analyzed by qPCR.Results: The IC۵۰ value of PCTL was ۱۰۰ μM and cytotoxic effectswere in a dose and time-dependent manner. Evaluation ofTM۴ Sertoli Cells morphology indicate that the cytotoxic concentrationsof PCTL were significantly higher than cisplatin.The results of PCR showed an increase in the expression of thep۶۲ dose-dependently in PCTL treated cells in compared to cisplatin.No significant difference was observed in the expressionof Atg۵ and Beclin۱ genes compared to the control group. Furthermore,BAX increasing and BCL۲ decreasing expression indicatingthe induction of apoptosis in treated PCTL TM۴ cells;however, higher doses of PCTL need to induce the apoptosis incompare to cisplatin.Conclusion: The results of the s tudy indicate that the PCTLhad less-lethal effects on TM۴ sertoli cells in compare to cisplatinand probably did not induce autophagy in TM۴ cells.

کلیدواژه ها:

Autophagy ، Cisplatin ، Gonadotoxicity ، Platinum-Based Anticancer Agents ، Sertoli TM۴ Cells