Modulatory Effect of Rutin on the Antitumor Activity and Genotoxicity of Cisplatin in Tumor-Bearing Mice

Abstract

Purpose: Cisplatin is a cancer chemotherapeutic drug that has been extensively used in the treatment of a variety of cancers. However, the full usage of cisplatin is limited due to its treatment associated development of multiple side effects in the host. In the present study, the modulatory effect of rutin, a type of flavonoid, on the cisplatin mediated antitumor activity and allied genotoxicity in ascites Dalton’s lymphoma (DL)-bearing mice were investigated. Methods: The antitumor activity was determined by calculating the percent increase in the life span of mice, cell viability and scanning electron microscopy of DL cells. Further, the modulatory effect of rutin on the cisplatin-induced genotoxic effects in the same DL-bearing mice was assessed by the analysis of micronuclei, chromosomal aberration and sperm abnormality. Results: The combination treatment of mice with rutin and cisplatin showed a considerable increase in the life span of the DL-bearing mice depicting better antitumor efficacy. Scanning electron microscopy of these DL cells showed severe membrane deformities in DL cells such as fusion of cell membrane, membrane blebbing, cell shrinkage, membrane folding and loss in microvilli from the tumor cell surface which may lead to cell death. Cisplatin alone treatment caused an increase in the frequency of chromosomal aberrations, micronuclei and sperms abnormality. However, the combination treatment of DL-bearing mice with rutin and cisplatin comparatively reduced these genotoxic effects. Conclusion: The overall findings suggest that rutin enhances the cisplatin-mediated antitumor activity and cytotoxicity against DL cells and at the same time diminishes the genotoxic effects induced by cisplatin in the DL-bearing mice.

Rutin Inhibits Hepatic and Pancreatic Cancer Cell Proliferation by Inhibiting CYP3A4 and GST

“…11 In addition, several reports showed that rutin protects against several tumor types, including lung, colorectal, cervical, prostate, breast, bladder, and breast cancer. [27][28][29][30][31][32][33][34] Rutin also causes cell cycle arrest, apoptosis, and inhibits the growth of human colon cancer cells, according to other studies. 27,30,32,[35][36][37] Rutin also affects cisplatin's anticancer efficacy and genotoxicity in tumor-bearing animals.…”

“…27,30,32,[35][36][37] Rutin also affects cisplatin's anticancer efficacy and genotoxicity in tumor-bearing animals. 33 Furthermore, rutin has been shown to promote autophagy mediated by p53 in human hepatoma Hep-G2 cells, while others have shown that rutin inhibits Sorafenib-induced Chemoresistance and Autophagy in hepatocellular carcinoma through modulating the BANCR/ miRNA-590-5P/OLR1 axis in hepatocellular carcinoma. 25,38 In spite of great efforts done, the detailed pharmacological actions of rutin on tumor cells is still needs to be further clarified.…”

Progress in the study of reproductive toxicity of platinum-based antitumor drugs and their means of prevention

“…Both drugs had a similar CA inducing capability and affected the mitotic index of the cells ( Azab et al, 2019 ). An escalation in the incidence of micronuclei in the peripheral blood cells of mice that underwent continuous injection of cisplatin was detected during the assay of micronuclei ( Prasad and Prasad, 2021 ).…”