Cytotoxic Constituents and Mechanism from Peganum harmala

Peganum harmala L. is a traditional Chinese and Uygur medicine used to treat cancer. Bioactivity-guided fractionation was applied to determine the cytotoxic constituents from P. harmala. A novel triterpenoid and a phenolic glycoside were isolated and identified, as well as seven known compounds. The novel metabolites were elucidated to be 3 alpha-acetoxy-27-hydroxyolean-12-en-28-oic acid methyl ester (1, OA) and N-acetyl-9-syringinoside (9). Some compounds exhibited potent cytotoxicity against human tumor cells. Among them, OA showed the highest cytotoxicity against human lung cancer cells A549 with an IC50 value of 8.03 +/- 0.81 mu M. OA had a potent anti-NSCLC cell activity by interfering with the epidermal growth factor receptor (EGFR) activation and its downstream signaling, and could exert an antiproliferative effect by inactivation of EGFR-driven antiapoptotic pathway followed by the release of mitochondrial cytochrome c, which might prove to be a promising leading compound for the development of an anti-lung cancer drug.