title: Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression.
abstract: Malignant melanoma is a destructive and lethal form of skin cancer with poor prognosis. An effective treatment for melanoma is greatly needed. Ginsenoside Rg3 is a herbal medicine with high antitumor activity. It is reported that abnormal glycosylation is correlated with the tumor cell growth. However, the antitumor effect of Rg3 on melanoma and its mechanism on regulating glycosylation are unknown. We found that Rg3 did not only inhibit A375 melanoma cell proliferation in a dose-dependent manner, but also decreased the expression of fucosyltransferase IV (FUT4) and its synthetic product Lewis Y (LeY), a tumor-associated carbohydrate antigen (TACA). Knocking down FUT4 expression by siRNA dramatically reduced FUT4/LeY level and inhibited cell proliferation through preventing the activation of EGFR/MAPK pathway. Consistently, the inhibitory effect of the Rg3 and FUT4 knockdown on melanoma growth was also seen in a xenograft melanoma mouse model. In conclusion, Rg3 effectively inhibited melanoma cell growth by downregulating FUT4 both in vitro and in vivo. Targeting FUT4/LeY mediated fucosylation by Rg3 inhibited the activation of EGFR/MAPK pathway and prevented melanoma growth. Results from this study suggest Rg3 is a potential novel therapy agent for melanoma treatment.
authors: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
authors: Xiu
authors: X
authors: Shan
authors: Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian Medical University, Dalian 116044, Liaoning, P.R. China.
authors: Faisal
authors: F
authors: Aziz
authors: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
authors: Li Li
authors: LL
authors: Tian
authors: Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Xiao Qi
authors: XQ
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Laboratory of Glycobiology and Glycoengineering, Dalian Medical University, Dalian 116044, Liaoning, P.R. China.
authors: Qiu
authors: Q
authors: Yan
authors: Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China.
authors: Ji Wei
authors: JW
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D036145:Ginsenosides / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000378:metabolism; D016256:Lewis X Antigen / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D036145:Ginsenosides; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; C094162:Lewis Y antigen; C097367:ginsenoside Rg3; C066693:FUT4 protein, human; D005647:Fucosyltransferases