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

作者：Carlos Romero Benavides Juan; Bailon Moscoso Natalia; Parra Delgado Hortensia; Isabel Ramirez Maria; Villacis Javier; Cabrera Henrry; Gonzalez Arevalo Gabriela; Cueva Ruth; Zentella Dehesa Alejandro; Ratovitski Edward A; Martinez Vazquez Mariano^*

来源：Medicinal Chemistry Research, 2018, 27(3): 834-843.

DOI：10.1007/s00044-017-2106-4

• Colon cancer
• Argentatin B
• Cell cycle arrest
• p73
• p53
• Genotoxicity

The 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 from Parthenium argentatum with inhibitory activity on tumor lines. The aim of this study is to investigate the inhibitory effect of 1 and 10 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 G(1) phase. The bromine 2 and oxime 6 derivatives were more active than 1. 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 than 6.

• 出版日期2018-3