8-Methoxypsoralen Induces Intrinsic Apoptosis in HepG2 Cells: Involvement of Reactive Oxygen Species Generation and ERK1/2 Pathway Inhibition

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Huan YangTao Xi

Abstract

8-Methoxypsoralen (8-MOP), a formerly considered photosensitizing agent, induces apoptosis when used alone. On this basis, the present study was designed to explore the effects and mechanisms of 8-MOP-induced apoptosis in human hepatocellular carcinoma HepG2 cells, independent of its photoactivation. 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. 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. 8...Continue Reading

Citations

Jan 26, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jing XiongJian Yang
Jun 22, 2018·ChemMedChem·Srinivasa Reddy BonamVijayapandi Pandy
Aug 13, 2020·International Journal of Molecular Sciences·Salman AhmedRaffaele Capasso
May 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aneta GrabarskaAndrzej Stepulak
Apr 20, 2018·Journal of Cellular Physiology·Keywan Mortezaee
Oct 28, 2017·Chemico-biological Interactions·Ju Ri HamMi-Kyung Lee

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