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Open AccessArticle

The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Korea
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Author to whom correspondence should be addressed.
Molecules 2020, 25(3), 501; https://doi.org/10.3390/molecules25030501
Received: 5 December 2019 / Revised: 15 January 2020 / Accepted: 21 January 2020 / Published: 23 January 2020
(This article belongs to the Special Issue Antitumor and Anti-HIV Agents from Natural Products)
Oxypeucedanin (OPD), a furocoumarin compound from Angelica dahurica (Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of OPD as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of OPD in SK-Hep-1 human hepatoma cells. OPD effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that OPD was able to induce G2/M phase cell cycle arrest in cells. The G2/M phase cell cycle arrest by OPD was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of OPD against hepatoma cells was found to be p53-dependent. The p53-expressing cells (SK-Hep-1 and HepG2) were sensitive, but p53-null cells (Hep3B) were insensitive to the antiproliferative activity of OPD. OPD also activated the expression of p53, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of OPD is in part correlated with the modulation of p53 in cancer cells. In addition, the combination of OPD with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of OPD may be highly associated with the induction of G2/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells. View Full-Text
Keywords: oxypeucedanin; Angelica dahurica; antiproliferation; G2/M phase cell cycle arrest; p53; SK-Hep-1; hepatoma cells oxypeucedanin; Angelica dahurica; antiproliferation; G2/M phase cell cycle arrest; p53; SK-Hep-1; hepatoma cells
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MDPI and ACS Style

Park, S.H.; Hong, J.-Y.; Park, H.J.; Lee, S.K. The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells. Molecules 2020, 25, 501. https://doi.org/10.3390/molecules25030501

AMA Style

Park SH, Hong J-Y, Park HJ, Lee SK. The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells. Molecules. 2020; 25(3):501. https://doi.org/10.3390/molecules25030501

Chicago/Turabian Style

Park, So H.; Hong, Ji-Young; Park, Hyen J.; Lee, Sang K. 2020. "The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells" Molecules 25, no. 3: 501. https://doi.org/10.3390/molecules25030501

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