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Ursolic Acid-Induced Apoptosis via Regulation of the PI3K/Akt and MAPK Signaling Pathways in Huh-7 Cells
Kwong-Chiu Lee1, Yao-Li Chen2,3,4, Ping-Yi Lin5
1Department of Anesthesiology, Changhua Christian Hospital, Changhua 50006, Taiwan. 75102@cch.org.tw.
Abstract:
Ursolic acid (UA), is a kind of triterpene acid that exhibits wide biological properties. In this article, the effects of UA on apoptosis and the proliferation of human hepatoma Huh-7 cells were reported. The MTT results showed that cell viability of Huh-7 was reduced in a concentration and time-dependent effect. In addition, DAPI staining was used to detected condensation of chromatin in nucleus. Apoptotic cell population was examined using Annexin V/PI staining. The results showed that exposure to UA affected extrinsic and intrinsic pathways through, reduced expression of Bcl-2, Mcl-1, and TCTP; increased levels of the apoptotic proteins TNF-α, Fas, FADD, and Bax; and activation of cleaved caspase-3 and PARP. UA also inhibited the p-Akt and p38 MAPK signaling transduction pathways, and increased activity in the p-ERK signaling pathway. Taken together, UA inhibited the cell growth of Huh-7 cells and affected apoptosis, via regulated cellular signaling transduction.
Insights
Ursolic acid (UA) effectively inhibits human hepatoma Huh-7 cell proliferation and induces apoptosis. This triterpene acid modulates key signaling pathways, offering potential therapeutic insights for liver cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Ursolic acid (UA) is a natural triterpene with diverse biological activities.
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Understanding the molecular mechanisms of natural compounds like UA in cancer is crucial.
Purpose of the Study:
- To investigate the effects of Ursolic acid (UA) on the proliferation and apoptosis of human hepatoma Huh-7 cells.
- To elucidate the underlying molecular signaling pathways modulated by UA.
Main Methods:
- Cell viability was assessed using MTT assays.
- Apoptosis was detected via DAPI staining and Annexin V/PI analysis.
- Protein expression levels and signaling pathway activation were analyzed.
Main Results:
- UA significantly reduced Huh-7 cell viability in a dose- and time-dependent manner.
- UA induced apoptosis by affecting both extrinsic and intrinsic pathways, altering Bcl-2 family proteins and activating caspases.
- UA modulated key signaling pathways, including inhibition of p-Akt and p38 MAPK, and activation of p-ERK.
Conclusions:
- Ursolic acid (UA) exhibits potent anti-proliferative and pro-apoptotic effects on human hepatoma Huh-7 cells.
- UA exerts its effects by regulating critical cellular signaling transduction pathways.
- UA demonstrates potential as a therapeutic agent for hepatocellular carcinoma.
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