title: Griffipavixanthone, a dimeric xanthone extracted from edible plants, inhibits tumor metastasis and proliferation via downregulation of the RAF pathway in esophageal cancer.
abstract: Metastasis causes a large number of deaths among esophageal cancer patients. The activation of RAF family proteins elevates tumor metastasis and proliferation. In screen targeting the RAF protein, we identified that Griffipavixanthone (GPX), a dimeric xanthone isolated from Garcinia esculenta, is a B-RAF and C-RAF inhibitor against esophageal cancer cells. Using wound healing, transwell migration and matrigel invasion assays, we confirmed that GPX significantly inhibited cell migration and invasion. Furthermore, exposure to GPX rendered cell proliferation and induced G2/M cell cycle arrest. Our mechanistic study showed that GPX suppressed cancer metastasis and proliferation through downregulation of RAF-MEK-ERK cascades proteins as well as RAF mRNA levels. In a pulmonary metastasis model, the intraperitoneal injection of GPX significantly suppressed esophageal tumor metastasis and ERK protein level in vivo. In conclusion, our present study suggested that GPX could inhibit tumor migration, invasion and proliferation in vitro and in vivo, which indicated the potential of GPX for preventing and treating esophageal cancer.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Ding
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Lao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Lunlun
authors.initials: L
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019281:Dimerization; D015536:Down-Regulation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D029760:Garcinia / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008819:Mice, Nude; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010945:Plants, Edible / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D048490:raf Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D010936:Plant Extracts; D044004:Xanthones; C000600533:griffipavixanthone; D048490:raf Kinases
keywords: Griffipavixanthone; RAF; esophageal cancer; metastasis; natural product