Elucidation of Glutathione-S-transferase Activity Induced by Pectin- Cisplatin Nano-conjugates for Optimization of New Therapeutic Strategies

Abstract

Despite tremendous efforts to search novel drugs and treatments, cancer continues to be a major health hazard. Modulation of cellular responses to platinating agents has important clinical implications as they are still heavily prescribed against various cancers. First line chemotherapeutic drug used for treating solid tumors, displays dose limiting nephrotoxicity. Natural products are being sought in order to improve the anticancer efficacy of cisplatin. Pectin, a plant polysaccharide have reported strong anti-oxidant and anti-cancer properties. In our study, Pectin-Cisplatin nanoconjugates in size range of (200 ± 20 nm) were synthesized and assessed for their anti-cancer and renoprotective role. The cytotoxicity of Pec-cis nanoconjugates and cis per se was assessed and co-related with the Glutathione-s-transferase level in both, in-vitro (B-16/F-10 mouse melanoma cell line) and in-vivo models (C57BL6 mice) in time (24 hours, 48 hours) and dose dependent (30 µg/ml and 60 µg/ml) manner. Our findings revealed that pectin-cisplatinnanoconjugates exhibited cytotoxicity similar to the cisplatin solution at 1/10th of the cisplatin content, which indicates a possible synergism between the activity of the cisplatin and pectin. MDA and histological findings were corraborated for altered renal function in tumor bearing mice. Enhanced GST level was reported post pectincisplatin nanoconjugates administration which confirmed that pectin-cisplatin treatment ameliorated both functional and histopathologic damage. This was further verified by lowered MDA levels when compared to cisplatinper se. Therefore, our results confirmed that Pectin-cisplatin nanoconjugates exhibited anti-tumor properties and rendered partial protection against cisplatin induced nephrotoxicity thereby proving the biocompatibility of pectin-cisplatin nanoconjugates for therapeutic purposes.