The Apoptotic Effect of Ursolic Acid on SK-Hep-1 Cells is Regulated by the PI3K/Akt, p38 and JNK MAPK Signaling Pathways.
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.
Transplant Medicine &amp; Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan. 159260@cch.org.tw.
Wan-Ling
WL
Chuang
Transplant Medicine &amp; Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan. 69221@cch.org.tw.
Ping-Yi
PY
Lin
Department of Nursing, Hung Kuang University, Taichung 43302, Taiwan. jenny9286@yahoo.com.tw.
Hui-Chuan
HC
Lin
Transplant Medicine &amp; Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan. 31560@cch.org.tw.|Department of Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan. 31560@cch.org.tw.|School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. 31560@cch.org.tw.
Yao-Li
YL
Chen
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000090324:Tumor Protein, Translationally-Controlled 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014315:Triterpenes; D000090324:Tumor Protein, Translationally-Controlled 1; D048051:p38 Mitogen-Activated Protein Kinases; D000097245:Ursolic Acid; C000715647:TPT1 protein, human
SK-Hep-1; apoptosis; ursolic acid