6,8-Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53
- Authors
- Choi, Y.J.; Lee, J.; Ha, S.H.; Lee, H.K.; Lim, H.M.; Yu, S.-H.; Lee, C.M.; Nam, M.J.; Yang, Y.-H.; Park, K.; Choi, Y.S.; Jang, K.Y.; Park, S.-H.
- Issue Date
- May-2021
- Publisher
- WILEY
- Keywords
- 6,8-diprenylorobol; apoptosis; colon cancer; p53; reactive oxygen species
- Citation
- ENVIRONMENTAL TOXICOLOGY, v.36, no.5, pp.914 - 925
- Journal Title
- ENVIRONMENTAL TOXICOLOGY
- Volume
- 36
- Number
- 5
- Start Page
- 914
- End Page
- 925
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/80686
- DOI
- 10.1002/tox.23093
- ISSN
- 1520-4081
- Abstract
- 6,8-Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8-diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8-diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8-Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose- and time-dependent manner. A 40 μM of 6,8-diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8-diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8-diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen-activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8-diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N-acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8-diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8-diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8-diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS. © 2020 Wiley Periodicals LLC.
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