9-Methoxycamptothecin (
MCPT) has been recently reported to have a strong anticancer activity. However, its detailed mechanism of action in human
cancer cells has not been well clarified. The results showed that
MCPT induced cytotoxicity in seven human
cancer cell lines in a dose dependent manner after 72h, with A2780 and Hela cell lines more sensitive, so the two cell lines were chosen to do further studies.
MCPT induced strong G2/M arrest in both A2780 cells and Hela cells after 24h, following by substantial sub-G1 arrest (indicating apoptosis). The apoptosis was verified by staining with
Annexin V-FITC and
propidium iodide. ROS generation increased significantly in
MCPT-induced apoptosis. Meanwhile, the apoptosis appeared to be dependent on
caspase-3, -8 and -9 in A2780 cells, and
caspase-3 in Hela cells. In addition,
MCPT induced up-regulation expression of most of seventeen genes in both cell lines. Western blot verified that changes of TNFα, Fas, P53 and P27
protein level were consistent with their gene expression changes. Taken together,
MCPT plays an important role in
tumor growth suppression by inducing apoptosis in both cell lines via extrinsic and intrinsic apoptotic pathways, and has the potential to be developed into an
antitumor agent.