Anti-cancer effect of liriodenine on human lung cancer cells.
Our previous work demonstrated that liriodenine, an isoquinoline alkaloid isolated from plant species of many genera, exhibits a potent cytotoxic effect on various types of human cancer cells. In this study, we investigated the effect of liriodenine on the growth and viability of human lung cancer cells and addressed the underlying mechanism of action. We found that liriodenine suppressed proliferation of A549 human lung adenocarcinoma cells in a dose- and time-dependent manner. Flow cytometric analysis showed that liriodenine blocked cell cycle progression at the G2/M phase. Induction of G2/M arrest by liriodenine was accompanied by reduction of G1 cyclin (D1) and accumulation of G2 cyclin (B1). In vitro kinase activity assay demonstrated that the enzymatic activity of the cyclin B1/cyclin-dependent kinase 1 complex was reduced in liriodenine-treated cells. More importantly, incubation with liriodenine led to activation of caspases and apoptosis in A549 cells. The apoptosis-inducing activity of liriodenine was more apparent when cells were cultured under serum-free conditions. Our results indicate that liriodenine exerts potent anti-proliferative and apoptosis-inducing effects on human lung cancer cells.
Chang
Hui-Chiu
HC
Department of Physiology and Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chang
Fang-Rong
FR
Wu
Yang-Chang
YC
Lai
Yung-Hsiung
YH
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001060:Aporphines / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology
D001060:Aporphines; D016895:Culture Media, Serum-Free; D010936:Plant Extracts; C026980:liriodenine; D018844:Cyclin-Dependent Kinases