Cytotoxic activity and G2/M cell cycle arrest mediated by antofine, a phenanthroindolizidine alkaloid isolated from Cynanchum paniculatum.

Starting with an extract derived from the root of Cynanchum paniculatum Kitagawa (Asclepiadaceae) that was active in the process of inhibiting the growth of human cancer cells in culture, a phenanthroindolizidine alkaloid antofine was isolated and identified as an active principle (IC50 = 7.0 +/- 0.2 ng/ml for A549, human lung cancer cells; IC50 = 8.6 +/- 0.3 ng/ml for Col2, human colon cancer cells). Prompted by the high potency of cancer cell growth inhibition, additional action mechanism studies were performed with antofine. Utilizing cultured Col2 cells as a model, antofine induced arrest in the G2/M phase of the cell cycle after 48 h of incubation. With wash-out experiment, colony formation was also inhibited in a dose-dependent manner. These data suggest the potential of antofine to serve as a cancer chemotherapeutic agent by virtue of arresting the cell cycle.