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Molecules 2016, 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

1
Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan
2
Department of Nursing, Hung Kuang University, Taichung 43302, Taiwan
3
Department of Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan
4
School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 8 March 2016 / Revised: 24 March 2016 / Accepted: 1 April 2016 / Published: 20 April 2016
(This article belongs to the Section Natural Products)
View Full-Text   |   Download PDF [4072 KB, uploaded 20 April 2016]   |  

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. View Full-Text
Keywords: apoptosis; ursolic acid; SK-Hep-1 apoptosis; ursolic acid; SK-Hep-1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Chuang, W.-L.; Lin, P.-Y.; Lin, H.-C.; Chen, Y.-L. The Apoptotic Effect of Ursolic Acid on SK-Hep-1 Cells is Regulated by the PI3K/Akt, p38 and JNK MAPK Signaling Pathways. Molecules 2016, 21, 460.

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