4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest
- Equal contributors
1 Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, Taiwan
2 School of Dentistry, Taipei Medical University, Taipei, Taiwan
3 Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan
4 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
5 Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan
6 Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan
7 Institute of Nutrition, China Medical University, Taichung, Taiwan
8 Institute of Molecular Medicine, National Tsing-Hua University, Hsinchu, Taiwan
9 Department of Life Science, National Tsing-Hua University, Hsinchu, Taiwan
10 School of Pharmacy, China Medical University, Taichung, Taiwan
11 Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
12 Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Kaohsiung, Taiwan
13 Graduate Institute of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan
14 Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
15 Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
BMC Cancer 2010, 10:46 doi:10.1186/1471-2407-10-46Published: 18 February 2010
The 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.
In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.