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 3α-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 μm. 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.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China.
Chunhua
C
Wang
College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang, 110142, P. R. China.
Zhenxue
Z
Zhang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China.
Yihai
Y
Wang
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China.
Xiangjiu
X
He
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D032443:Peganum / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
3α-Acetoxy-27-hydroxyolean-12-en-28-oic acid methyl ester; Cytotoxic activity; Non-small cell lung cancer; Peganum harmala; Triterpenoids