Plumbagin from a tropical pitcher plant (Nepenthes alata Blanco) induces apoptotic cell death via a p53-dependent pathway in MCF-7 human breast cancer cells.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthaquinone) has displayed antitumor activity in vitro and in animal models; however, the underlying molecular mechanisms have not been fully explored. The aim of this study was to investigate the anticancer effects of plumbagin isolated from Nepenthes alata against MCF-7 breast cancer cells. We examined the cytotoxicity, cell cycle regulation, apoptotic cell death, and generation of intracellular reactive oxygen species (ROS) in MCF-7 cells. Plumbagin exhibited potent cytotoxicity in MCF-7 cells (wild-type p53) compared to that in SK-OV-3 (null-type) human epithelial ovarian cancer cells. Specifically, plumbagin upregulated the expression of p21CIP1/WAF1 in MCF-7 cells, causing cell cycle arrest in the G2/M phase through inhibition of cyclin B1 levels. Plumbagin also significantly increased the ratio of Bax/Bcl-2 and release of cytochrome c, resulting in apoptotic cell death in MCF-7 cells. Furthermore, plumbagin dramatically increased the intracellular ROS level, whereas pretreatment with the ROS scavenger N-acetyl cysteine protected against plumbagin-induced cytotoxicity, suggesting that ROS formation plays a pivotal role in antitumor activity in MCF-7 cells. In mice bearing MCF-7 cell xenografts, plumbagin significantly reduced tumor growth and weight without apparent side effects. We therefore concluded that plumbagin exerts anticancer activity against MCF-7 cells through the generation of intracellular ROS, resulting in the induction of apoptosis via a p53-dependent pathway. This study thus identifies a new anticancer mechanism of plumbagin against p53-dependent breast cancer cells and suggests a novel strategy for overcoming of breast cancer therapy.

Antiviral effect of flavonol glycosides isolated from the leaf of Zanthoxylum piperitum on influenza virus.

The ethanol extract of Zanthoxylum piperitum (L.) DC. showed in vitro antiviral activity against influenza A virus. Three flavonol glycosides were isolated from the EtOAc fraction of Z. piperitum leaf by means of activity-guided chromatographic separation. Structures of isolated compounds were identified as quercetin 3-O-ß-D-galactopyranoside (1), quercetin 3-O-α-L-rhamnopyranoside (2), kaempferol 3-O-α-L-rhamnopyranoside (3) by comparing their spectral data with literature values. The anti-influenza viral activity of isolates was evaluated using a plaque reduction assay against influenza A/NWS/33 (H1N1) virus. The compounds also were subjected to neuraminidase inhibition assay in influenza A/NWS/33 virus. Compounds 1-3 exhibited antiviral activity against an influenza A virus in vitro, and inhibited the neuraminidase activity at relatively high concentrations.