The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

Oxypeucedanin (OPD), a furocoumarin compound from <i>Angelica dahurica</i> (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...

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Main Authors: So Hyun Park, Ji-Young Hong, Hyen Joo Park, Sang Kook Lee
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Molecules
Subjects:
oxypeucedanin
<i>angelica dahurica</i>
antiproliferation
g<sub>2</sub>/m phase cell cycle arrest
p53
sk-hep-1
hepatoma cells
Online Access:https://www.mdpi.com/1420-3049/25/3/501
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spelling doaj-79399fcc435b4dc5baca15c39f7a32342020-11-25T02:20:24ZengMDPI AGMolecules1420-30492020-01-0125350110.3390/molecules25030501molecules25030501The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma CellsSo Hyun Park0Ji-Young Hong1Hyen Joo Park2Sang Kook Lee3College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaCollege of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, KoreaOxypeucedanin (OPD), a furocoumarin compound from <i>Angelica dahurica</i> (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 G<sub>2</sub>/M phase cell cycle arrest in cells. The G<sub>2</sub>/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 G<sub>2</sub>/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.https://www.mdpi.com/1420-3049/25/3/501oxypeucedanin<i>angelica dahurica</i>antiproliferationg<sub>2</sub>/m phase cell cycle arrestp53sk-hep-1hepatoma cells
collection DOAJ
language English
format Article
sources DOAJ
author So Hyun Park
Ji-Young Hong
Hyen Joo Park
Sang Kook Lee
spellingShingle So Hyun Park
Ji-Young Hong
Hyen Joo Park
Sang Kook Lee
The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells
Molecules
oxypeucedanin
<i>angelica dahurica</i>
antiproliferation
g<sub>2</sub>/m phase cell cycle arrest
p53
sk-hep-1
hepatoma cells
author_facet So Hyun Park
Ji-Young Hong
Hyen Joo Park
Sang Kook Lee
author_sort So Hyun Park
title The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells
title_short The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells
title_full The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells
title_fullStr The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells
title_full_unstemmed The Antiproliferative Activity of Oxypeucedanin via Induction of G<sub>2</sub>/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells
title_sort antiproliferative activity of oxypeucedanin via induction of g<sub>2</sub>/m phase cell cycle arrest and p53-dependent mdm2/p21 expression in human hepatoma cells
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2020-01-01
description Oxypeucedanin (OPD), a furocoumarin compound from <i>Angelica dahurica</i> (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 G<sub>2</sub>/M phase cell cycle arrest in cells. The G<sub>2</sub>/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 G<sub>2</sub>/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.
topic oxypeucedanin
<i>angelica dahurica</i>
antiproliferation
g<sub>2</sub>/m phase cell cycle arrest
p53
sk-hep-1
hepatoma cells
url https://www.mdpi.com/1420-3049/25/3/501
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