Abstract | BACKGROUND/AIMS: METHODS: We analyzed the cell viability with MTT assay. Flow cytometry was used to examine the apoptosis rate, mitochondrial membrane potential ( MMP) and reactive oxygen species (ROS) generation after specific staining. The expression and location of apoptosis-associated protein as well as the activation status of cell signaling pathway were determined by Western blot analysis. RESULTS:
8-MOP significantly decreased cell viability and induced cell apoptosis through mitochondrial apoptotic pathway, as demonstrated by increased Bax/Bcl-2 ratio, collapsed MMP, and induced cytochrome c release (Cyt c) and apoptosis-inducing factor (AIF) transposition. ROS generation was significantly increased by 8-MOP and the eradication of ROS significantly abolished 8-MOP-induced apoptosis. In addition, the activation of ERK1/2 was drastically decreased by 8-MOP as ERK inhibitor PD98059, indicating a role of ERK1/2 signaling pathway in 8-MOP-induced cell apoptosis. CONCLUSION:
8-MOP induces intrinsic apoptosis by increasing ROS generation and inhibiting ERK1/2 pathway in HepG2 cells. The findings are important in substantiating the anti- tumor role of 8-MOP in cancer therapy.
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Authors | Huan Yang, Jing Xiong, Wenjing Luo, Jian Yang, Tao Xi |
Journal | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
(Cell Physiol Biochem)
Vol. 37
Issue 1
Pg. 361-74
( 2015)
ISSN: 1421-9778 [Electronic] Germany |
PMID | 26316083
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 S. Karger AG, Basel. |
Chemical References |
- Apoptosis Inducing Factor
- Reactive Oxygen Species
- bcl-2-Associated X Protein
- Cytochromes c
- Methoxsalen
|
Topics |
- Apoptosis
(drug effects)
- Apoptosis Inducing Factor
(metabolism)
- Carcinoma, Hepatocellular
(drug therapy, metabolism)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cytochromes c
(metabolism)
- HCT116 Cells
- Hep G2 Cells
- Humans
- Liver Neoplasms
(drug therapy, metabolism)
- MAP Kinase Signaling System
(drug effects)
- MCF-7 Cells
- Membrane Potential, Mitochondrial
(drug effects)
- Methoxsalen
(pharmacology)
- Mitochondria
(drug effects, metabolism)
- Reactive Oxygen Species
(metabolism)
- Signal Transduction
(drug effects)
- bcl-2-Associated X Protein
(metabolism)
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