title: Blockade of epidermal growth factor receptor/mammalian target of rapamycin pathway by Icariside II results in reduced cell proliferation of osteosarcoma cells.
abstract: Icariside II is considered one of the most important natural flavonoids with multiple bioactivities from traditional Chinese medicine Yin Yanghuo (YYH) or Horny Goat Weed (Epimedium koreanum Nakai). Previous studies show that Icariside II exhibits potent cytotoxicity against a broad spectrum of human cancer cells through various signaling transduction pathways. However, there are few reports about the effect of Icariside II on osteosarcoma cell. In this study, we found that Icariside II decreased cell proliferation in human osteosarcoma MG-63 cells and human osteosarcoma Saos-2 cells. In addition, Icariside II inactivated EGFR/mTOR signaling pathway, including EGFR, PI3K/AKT/PRAS40, Raf/MEK/ERK as well as mTOR. Furthermore, Icariside II inhibited epidermal growth factor (EGF)-induced activation of EGFR/mTOR signaling pathway. Pretreatment of EGF partially reversed cell viability decreased by Icariside II. Importantly, Icariside II inhibited the proliferation of transplantable tumors and EGFR/mTOR signaling pathway in sarcoma-180 bearing mice. In summary, these results indicate that Icariside II inhibits the proliferation of osteosarcoma cells in vitro and in vivo via EGFR/mTOR signaling pathway.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ya-di
authors.initials: YD
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpu_lykong@126.com.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D005419:Flavonoids; C060988:baohuoside I; C546842:MTOR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases
keywords: Anti-proliferation; EGFR; Icariside II; Osteosarcoma cells; mTOR