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Chemico-Biological Interactions 2009-Jul

The in vitro and in vivo apoptotic effects of Mahonia oiwakensis on human lung cancer cells.

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Bing-Sang Wong
Yung-Chin Hsiao
Ta-Wei Lin
Kuo-Shuen Chen
Pei-Ni Chen
Wu-Hsien Kuo
Shu-Chen Chu
Yih-Shou Hsieh

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Both the root and stem bark of Mahonia species were popular folk medicines. The plant has several proven biological activities including anti-bacterial, anti-fungal, and anti-inflammatory effects. However, Mahonia has not been studied for its anticancer effects. In the present study, we made extracts from Mahonia oiwakensis (MOE), a selected species in Taiwan, and investigated their effects on various human lung cells. We found that MOE-induced apoptotic death in human A549 non-small-cell lung carcinoma (NSCLC) cells in a dose- and time-dependent manner. Treatment with the extracts also caused an increase in the sub-G1 fraction of cells, chromosome condensation, and DNA fragmentation. The mitochondrial-mediated pathway was implicated in this MOE-induced apoptosis as evidenced by the activation of the caspase cascade, cleavage of poly (ADP-ribose) polymerase (PARP), disruption of mitochondrial membrane potential, and release of cytochrome C. A higher ratio of Bax/Bcl-2 proteins and cleavage of Bid were also observed in MOE-induced cell apoptosis. In A549 tumor-xenografted nude mice, MOE also retarded in vivo proliferation (P<0.05) and induced apoptosis in tumor cells, as shown by a decrease in Ki-67-positive staining (P<0.05) and increased transferase-mediated dUTP nick-end labeling (TUNEL)-positive staining (P<0.05). In conclusion, MOE inhibits the growth of human lung cancer cells in vitro and in vivo, suggesting that it may have therapeutic potential against human lung cancer.

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