Acovenoside A as a novel therapeutic approach to boost taxol and carboplatin apoptotic and antiproliferative activities in NSCLC: Interplay of miR-630/miR- 181a and apoptosis genes

Abstract

The aim of the present study is to explore the potential anticancer effect of the cardenolide; 2 acovenoside A against non-small cell lung cancer, understand its molecular mechanism in inducing 3 apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the 4 combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the 5 synergistic effect. The triple combination showed the best growth inhibition efficiency where the 6 number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The 7 combination also showed the most remarkable increase in gene expression of Bax and p53 and the least 8 level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell 9 lines treated with the combination. The present study has proven that the underlying mechanism of 10 acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions 11 which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present 12 study is the first to address the valuable effect of using acovenoside A together with carboplatin and 13 taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic ef