6,8-Diprenylorobol induces apoptosis in human colon cancer cells via activation of intracellular reactive oxygen species and p53

  • Environ Toxicol. 2021 May;36(5):914-925. doi: 10.1002/tox.23093.
Yong Jun Choi  1 ,  Jongsung Lee  2 ,  Sang Hoon Ha  3 ,  Han Ki Lee  4 ,  Heui Min Lim  4 ,  Seon-Hak Yu  1 ,  Chang Min Lee  1 ,  Myeong Jin Nam  4 ,  Yung-Hun Yang  5 ,  Kyungmoon Park  1 ,  Youn Soo Choi  6  7 ,  Kyu Yun Jang  8  9  10 ,  See-Hyoung Park  1
Affiliations
  • 1. Department of Bio and Chemical Engineering, Hongik University, Sejong, South Korea.
  • 2. Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, South Korea.
  • 3. Division of Biotechnology, Jeonbuk National University, Iksan, South Korea.
  • 4. Department of Biological Science, Gachon University, Seongnam, South Korea.
  • 5. Department of Biological Engineering, Konkuk University, Seoul, South Korea.
  • 6. Department of Biomedical Sciences, Seoul National University, Graduate School, Seoul, South Korea.
  • 7. Department of Medicine, College of Medicine, Seoul National University, Seoul, South Korea.
  • 8. Department of Pathology, Jeonbuk National University Medical School, Jeonju, South Korea.
  • 9. Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju, South Korea.
  • 10. Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea.
PMID: 33382531 DOI: 10.1002/tox.23093
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.

Keywords
6,8-diprenylorobol; apoptosis; colon cancer; p53; reactive oxygen species.
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