title: A novel mechanism for momordin Ic-induced HepG2 apoptosis: involvement of PI3K- and MAPK-dependent PPARγ activation.
abstract: Momordin Ic is a natural triterpenoid saponin found in various Chinese and Japanese natural medicines such as the fruit of Kochia scoparia (L.) Schrad. Momordin Ic has been previously demonstrated to induce HepG2 cell apoptosis in a ROS-mediated PI3K and MAPK pathway-dependent manner. In the present study, the underlying mechanisms of PI3K and MAPK pathway-mediated PPARγ, and PGC-1α co-regulator activation, as well as the effects of downstream proteins, COX-2 and FoxO4, on cell apoptosis were investigated. The results demonstrated that momordin Ic activated PPARγ and inhibited COX-2. PGC-1α and FoxO4 expressions were increased by the PI3K or MAPK pathways. Furthermore, PPARγ inhibition decreased p-p38 and FoxO4 expression, and restored COX-2 expression. ROS inhibition exerted little effect on PPARγ, COX-2 and FoxO4 expression but affected PGC-1α expression. These results revealed the involvement of PI3K and MAPK-dependent PPARγ activation in momordin Ic-induced apoptosis, providing more detailed information underlying the pro-apoptotic mechanism of momordin Ic in HepG2 cell apoptosis.
authors.affiliation: College of Food Science and Engineering, Northwest A&F University, Yangling 712100, Shaanxi, China. xueboliu@aliyun.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.forename: Haifang
authors.initials: H
authors.lastname: Xiao
authors.forename: Chan
authors.initials: C
authors.lastname: Wang
authors.forename: Chunxia
authors.initials: C
authors.lastname: Xiao
authors.forename: Yutang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xuebo
authors.initials: X
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D027467:Bassia scoparia / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047495:PPAR gamma; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C548297:momordin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019869:Phosphatidylinositol 3-Kinases