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

Abstract

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.

Novel read‐through fusion transcript Bcl2l2‐Pabpn1 in glioblastoma cells

“…Given that the cell cycle plays a vital role in cell proliferation, 38 flow cytometric analysis was performed to measure the cell cycle distribution. Downregulation of Bcl2l2‐Pabpn1 arrested the cell cycle at the G2‐M phase in glioblastoma cells (Figure 4F,G), indicating that reduced proliferation activity induced by Bcl2l2‐Pabpn1 deficiency might be related to G2‐M phase cell cycle arrest 39 . Additionally, cell apoptosis was significantly promoted by Bcl2l2‐Pabpn1 knockdown using flow cytometry (Figure 4H,I).…”

“…Downregulation of Bcl2l2-Pabpn1 arrested the cell cycle at the G2-M phase in glioblastoma cells (Figure 4F,G), indicating that reduced proliferation activity induced by Bcl2l2-Pabpn1 deficiency might be related to G2-M phase cell cycle arrest. 39 Additionally, cell apoptosis was significantly promoted by Bcl2l2-Pabpn1 knockdown using flow cytometry (Figure 4H,I). We further explored whether Bcl2l2-Pabpn1 participates in the motility of glioblastoma cells.…”

Oxypeucedanin: Chemotaxonomy, Isolation, and Bioactivities

“…Column chromatography on silica gel (CC) has been used for the isolation of OP from the root methanolic fraction of A. dahurica [ 16 , 17 , 18 ]. This compound has been isolated from ethanolic and n -butanol (BuOH)-soluble partitions of this species by exploiting CC [ 19 ] and recrystallization [ 20 ], respectively; as well as from the CHCl 3 and CH 2 Cl 2 soluble fractions using CC [ 21 ] and recrystallization methods [ 22 ], and CC on silica gel [ 23 , 24 ], respectively.…”

Preclinical Pharmacokinetics and Bioavailability of Oxypeucedanin in Rats after Single Intravenous and Oral Administration

“…Notably, the root part of ADR has been characterized as the richest natural source of oxypeucedanin [ 6 ]. Previous studies have indicated that oxypeucedanin have various biological activities including antiarrhythmic activity, anti-oxidant, anti-inflammatory, analgesic, anti-cancer, and antibacterial effects [ 6 , 7 , 8 , 9 ]. Furthermore, oxypeucedanin was reported to be a potentially effective intervention for nephrotoxicity induced by sunitinib [ 10 ].…”