* Contributed equally
BMC Cancer 2010, 10:46 doi:10.1186/1471−2407−10−46The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti−hepatoma and anti−inflammatory activities. However, the cellular mechanism involved in this process is still unknown.
Herein, we isolated the main pure compound, 4β−Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet−nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.
It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose−dependent manner (p < 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose− and time−dependent manners (p < 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub−G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double−staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h.
ConclusionsIn this study, we demonstrated that golden berry−derived 4βHWE is a potential DNA−damaging and chemotherapeutic agent against lung cancer.
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