Invitro anticancer effects of two novel phenanthroindolizidine alkaloid compounds on human colon and liver cancer cells.

Abstract

Malignant cancer is one of the most serious diseases threatening the health of human beings. Natural plant alkaloids exhibit multiple biological functions, including inhibition of cell proliferation, and may have potential anticancer activity. However, most natural alkaloids may not be suitable for human therapies owing to instability, poor dissolubility and potential side effects. To improve their anticancer activity and drug effect, the present study aimed to develop new alkaloid derivatives, the phenanthroindolizidine alkaloid compounds, and evaluated their potential antitumor effects on human cancer cells in vitro. Among the several newly synthesized analogues of phenanthroindolizidine alkaloids (PAs), the compounds YS306 and YS206 exhibited an increased growth inhibition activity on HepG2 liver cancer cells and on HCT116 and HT29 colon cancer cells, with half-maximal inhibitory concentrations in the micromolar range. YS206 and YS306 (5 µg/ml) both significantly induced cell cycle arrest at the G2/M phase and notably decreased cell distribution at the G0/G1 and S phase. In addition, these two molecules significantly inhibited cancer cell migration, as analyzed by the wound-healing and Transwell assays. However, neither YS306 nor YS206 exhibited observable effects on apoptosis. Therefore, chemical structure modifications of natural PAs based on anticancer activity assessments may be feasible in the development of new cancer chemotherapeutic agents.