Based on the potential of natural products as a source for the development of
cancer chemotherapeutic agents, this study was performed to investigate the anti-proliferative and antitumor effects of
antofine, a
phenanthroindolizidine alkaloid derived from Cynanchum paniculatum.
Antofine showed potent anti-proliferative effects in several human
cancer cells with IC(50) values in the nanomolar range. Treatment with
antofine for 24h did not result in the induction of apoptotic cell death but moderately induced cell cycle arrest at G0/G1 phase and inhibited the expression of
cyclin D1,
cyclin E, and CDK4. In addition,
antofine inhibited the transcriptional activity of β-
catenin/Tcf in human colon HCT 116 cells, and the expression level of β-
catenin and
cyclin D1 was also down-regulated by
antofine in human colon SW480 cells. Moreover,
antofine potentiated
tumor necrosis factor-α (TNF-α)-induced apoptosis, which was demonstrated by the increase of
Annexin V-positive cell population and of the cleavage of
poly (ADP-ribose) polymerase (PARP) and
caspase-8.
Antofine also effectively suppressed
tumor growth in the HCT 116 implanted xenograft nude mouse model. Taken together, these findings suggest that
antofine might be a potential candidate for the development of
cancer chemotherapeutic agents derived from natural products.