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Molecules. 2016 Apr 20;21(4):460. doi: 10.3390/molecules21040460.

The Apoptotic Effect of Ursolic Acid on SK-Hep-1 Cells is Regulated by the PI3K/Akt, p38 and JNK MAPK Signaling Pathways.

Author information

1
Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan. 159260@cch.org.tw.
2
Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan. 69221@cch.org.tw.
3
Department of Nursing, Hung Kuang University, Taichung 43302, Taiwan. jenny9286@yahoo.com.tw.
4
Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan. 31560@cch.org.tw.
5
Department of Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan. 31560@cch.org.tw.
6
School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. 31560@cch.org.tw.

Abstract

Ursolic acid (UA) is a pentacyclic triterpene acid that is present in a wide variety of medicinal herbs and edible plants. This study investigated the effect of UA on apoptosis and proliferation of hepatocellular carcinoma SK-Hep-1 cells. After treatment of SK-Hep-1 cells with different concentrations of UA, we observed that cell viability was reduced in a dose- and time-dependent manner. Furthermore, there was a dose-dependent increase in the percentage of cells in the sub-G1 and G2/M phases, with cells treated with 60 μM showing the highest percentages of cells in those phases. UA-induced chromatin condensation of nuclei was observed by using DAPI staining. The western blot results revealed that exposure to UA was associated with decreased expression of the anti-apoptotic proteins Mcl-1, Bcl-xL, Bcl-2, and TCTP and increased expression of apoptosis-related proteins TNF-α, Fas, FADD, Bax, cleaved caspase-3, caspase-8, caspase-9, and PARP. Immunocytochemistry staining showed that treatment with UA resulted in increased expression of caspase-3. Moreover, exposure to UA resulted in the inhibition of the PI3K/Akt and p38 MAPK signaling pathways. These findings suggest that UA inhibits the proliferation of SK-Hep-1 cells and induces apoptosis.

KEYWORDS:

SK-Hep-1; apoptosis; ursolic acid

PMID:
27104510
PMCID:
PMC6274268
DOI:
10.3390/molecules21040460
[Indexed for MEDLINE]
Free PMC Article

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