Journal of Microbiology and Biotechnology

  • 제31권12호
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  • Pages.1615-1623
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  • 2021
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Picropodophyllotoxin Induces G1 Cell Cycle Arrest and Apoptosis in Human Colorectal Cancer Cells via ROS Generation and Activation of p38 MAPK Signaling Pathway

  • Lee, Seung-On (Department of Biomedicine, Health and Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University) ;
  • Kwak, Ah-Won (Department of Pharmacy, College of Pharmacy, Mokpo National University) ;
  • Lee, Mee-Hyun (College of Korean Medicine, Dongshin University) ;
  • Seo, Ji-Hye (Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University) ;
  • Cho, Seung-Sik (Department of Biomedicine, Health and Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University) ;
  • Yoon, Goo (Department of Pharmacy, College of Pharmacy, Mokpo National University) ;
  • Chae, Jung-Il (Department of Dental Pharmacology, School of Dentistry, Jeonbuk National University) ;
  • Joo, Sang Hoon (College of Pharmacy, Daegu Catholic University) ;
  • Shim, Jung-Hyun (Department of Biomedicine, Health and Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University)
  • 투고 : 2021.09.07
  • 심사 : 2021.09.13
  • 발행 : 2021.12.28
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초록

Picropodophyllotoxin (PPT), an epimer of podophyllotoxin, is derived from the roots of Podophyllum hexandrum and exerts various biological effects, including anti-proliferation activity. However, the effect of PPT on colorectal cancer cells and the associated cellular mechanisms have not been studied. In the present study, we explored the anticancer activity of PPT and its underlying mechanisms in HCT116 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to monitor cell viability. Flow cytometry was used to evaluate cell cycle distribution, the induction of apoptosis, the level of reactive oxygen species (ROS), assess the mitochondrial membrane potential (Δψm), and multi-caspase activity. Western blot assays were performed to detect the expression of cell cycle regulatory proteins, apoptosis-related proteins, and p38 MAPK (mitogen-activated protein kinase). We found that PPT induced apoptosis, cell cycle arrest at the G1 phase, and ROS in the HCT116 cell line. In addition, PPT enhanced the phosphorylation of p38 MAPK, which regulates apoptosis and PPT-induced apoptosis. The phosphorylation of p38 MAPK was inhibited by an antioxidant agent (N-acetyl-L-cysteine, NAC) and a p38 inhibitor (SB203580). PPT induced depolarization of the mitochondrial inner membrane and caspase-dependent apoptosis, which was attenuated by exposure to Z-VAD-FMK. Overall, these data indicate that PPT induced G1 arrest and apoptosis via ROS generation and activation of the p38 MAPK signaling pathway.

키워드

과제정보

We greatly appreciated using the Convergence Research Laboratory (established by the MNU Innovation Support Project in 2019) to conduct this research. This research was funded by the Basic Science Research Program of National Research Foundation Korea, grant number 2019R1A2C1005899.

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