title: Phloridzin isolated from Acanthopanax senticosus promotes proliferation of α6 integrin (CD 49f) and β1 integrin (CD29) enriched for a primary keratinocyte population through the ERK-mediated mTOR pathway.
abstract: We investigated the proliferative effect of a Acanthopanax senticosus extract (ASE) on human CD49f(+)/CD29(+) keratinocytes and isolated phloridzin from A. senticosus as an active compound. In addition, the possible mechanisms of action were examined. We found that the ASE and phloridzin-promoted proliferation of CD49f(+)/CD29(+) cells using MTT and Click-iT™ EdU flow cytometry assays. In addition, phosphorylation of the p44/42 MAPK (ERK), mTOR, p70 S6 kinase (p70S6K), S6 ribosomal protein (S6RP), eukaryotic initiation factor 4B (eIF4B), and eIF4E was stepwise induced in CD49f(+)/CD29(+) cells. Furthermore, the ASE and phloridzin significantly induced the production of vascular endothelial growth factor and interleukin-6 in CD49f(+)/CD29(+) cells. Similarly, ASE and phloridzin-induced phosphorylation of the mTOR/p70S6K/S6RP/eIF4B/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Taken together, these results indicate that ASE and phloridzin-induced proliferation of CD49f(+)/CD29(+) cells under serum-free conditions was mediated by the ERK-dependent mTOR pathway.
authors.affiliation: Biospectrum Life Science Institute, Seongnam City, Gyunggi Do, 462-807, Republic of Korea.
authors.forename: Jienny
authors.initials: J
authors.lastname: Lee
authors.forename: Eunsun
authors.initials: E
authors.lastname: Jung
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Park
authors.forename: Kazumi
authors.initials: K
authors.lastname: Toyama
authors.forename: Akira
authors.initials: A
authors.lastname: Date
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D028001:Eleutherococcus; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D052816:Foreskin / Q000166:cytology; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D010695:Phlorhizin / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D005419:Flavonoids; D039503:Integrin alpha6; D019012:Integrin beta1; D010936:Plant Extracts; C031799:eIF-4B; D010695:Phlorhizin; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one