Argentatin B derivatives induce cell cycle arrest and DNA damage in human colon cancer cells through p73/p53 regulation

AbstractThe unique etiology of cancer requires a multidimensional approach for its treatment, control, and prevention. Therefore, all approaches to drug discovery and development should be exploited. Argentatin B (1) is a cycloartane triterpene isolated fromParthenium argentatum with inhibitory activity on tumor lines. The aim of this study is to investigate the inhibitory effect of1 and10 derivatives on the proliferation of a human colon cancer cell line (RKO), their genotoxic effects on human lymphocytes, as well as their potential effect on tumor protein (TP)-p53 and TP73 expression and phosphorylation. Argentatin B was found to induce reduced survival of RKO cells and showed a cytostatic effect. However, it did not induce apoptosis of RKO cells at the concentrations tested. Argentatin B and its derivatives were found to arrest the cell cycle at the G1 phase. The bromine2 and oxime6 derivatives were more active than1. Furthermore,1 and its bromine (2) and oxime (6) derivatives induced phosphorylation of (TP)-p53 and TP73. Nevertheless,2 exhibited a greater genotoxic effect on normal human lymphocytes than6.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research