title: Modified Panax ginseng Extract Inhibits uPAR-Mediated α[Formula: see text]β1-Integrin Signaling by Modulating Caveolin-1 to Induce Early Apoptosis in Lung Cancer Cells.
abstract: Urokinase receptor (uPAR) is enhanced in many human cancer cells and is frequently an indicator of poor prognosis. Activation of [Formula: see text]1-integrin requires caveolin-1 and is regulated by uPAR. However, the underlying molecular mechanism responsible for the interaction between uPAR and [Formula: see text]1-integrin remains obscure. We found that modified regular Panax ginseng extract (MRGX) had a negative modulating effect on the uPAR/[Formula: see text]1-integrin interaction, disrupted the uPAR/integrin interaction by modulating caveoline-1, and caused early apoptosis in cancer cells. Additionally, we found that siRNA-mediated caveoline-1 downregulation inhibited uPAR-mediated [Formula: see text]1-integrin signaling, whereas caveoline-1 up-regulation stimulated the signaling, which suppressed p53 expression, thereby indicating negative crosstalk exists between the integrin [Formula: see text]1 and the p53 pathways. Thus, these findings identify a novel mechanism whereby the inhibition of [Formula: see text]1 integrin and the activation of p53 modulate the expression of the anti-apoptotic proteins that are crucially involved in inducing apoptosis in A549 lung cancer cells. Furthermore, MRGX causes changes in the expressions of members of the Bcl-2 family (Bax and Bcl-2) in a pro-apoptotic manner. In addition, MGRX-mediated inhibition of [Formula: see text]1 integrin attenuates ERK phosphorylation (p-ERK), which up-regulates caspase-8 and Bax. Therefore, ERK may affect mitochondria through a negative regulation of caspase-8 and Bax. Taken together, these findings reveal that MRGX is involved in uPAR-[Formula: see text]1-integrin signaling by modulating caveolin-1 signaling to induce early apoptosis in A549 lung-cancer cells and strongly indicate that MRGX might be useful as a herbal medicine and may lead to the development of new herbal medicine that would suppress the growth of lung-cancer cells.
authors.affiliation: * Department of Physiology, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
authors.forename: In-Hu
authors.initials: IH
authors.lastname: Hwang
authors.affiliation: † East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea.
authors.forename: Yong-Kyun
authors.initials: YK
authors.lastname: Kwon
authors.affiliation: † East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea.
authors.forename: Chong-Kwan
authors.initials: CK
authors.lastname: Cho
authors.affiliation: † East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea.
authors.forename: Yeon-Weol
authors.initials: YW
authors.lastname: Lee
authors.affiliation: ‡ Department of Life Science, Dongguk University, Goyang, Gyeonggi-do 10326, Republic of Korea.
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Sung
authors.affiliation: § Department of Sasang Constitutional Medicine, Wonkwang University Oriental Medical Hospital, Jeonju 54887, Republic of Korea.
authors.forename: Jong-Cheon
authors.initials: JC
authors.lastname: Joo
authors.affiliation: ¶ Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Korea.
authors.forename: Kyung-Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: † East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea.
authors.forename: Hwa-Seung
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: ¶ Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Korea.
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051242:Caveolin 1; D039081:Integrin alpha5beta1; D010936:Plant Extracts; D055293:Receptors, Urokinase Plasminogen Activator; D053181:Caspase 8
keywords: Caveoline-1; Early Apoptosis; Integrin 1; MRGX; uPAR