title: Guttiferone K suppresses cell motility and metastasis of hepatocellular carcinoma by restoring aberrantly reduced profilin 1.
abstract: Hepatocellular carcinoma (HCC) is an aggressive malignancy and the 5-year survival rate of advanced HCC is < 10%. Guttiferone K (GUTK) isolated from the Garcinia genus inhibited HCC cells migration and invasion in vitro and metastasis in vivo without apparent toxicity. Proteomic analysis revealed that actin-binding protein profilin 1 (PFN1) was markedly increased in the presence of GUTK. Over-expression of PFN1 mimicked the effect of GUTK on HCC cell motility and metastasis. The effect of GUTK on cell motility was diminished when PFN1 was over-expressed or silenced. Over-expression of PFN1 or incubation with GUTK decreased F-actin levels and the expression of proteins involved in actin nucleation, branching and polymerization. Moreover, a reduction of PFN1 protein levels was common in advanced human HCC and associated with poor survival rate. In conclusion, GUTK effectively suppresses the motility and metastasis of HCC cells mainly by restoration of aberrantly reduced PFN1 protein expression.
authors: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Kaikai
authors: K
authors: Shen
authors: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors: Zhichao
authors: Z
authors: Xi
authors: Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, Australia.
authors: Jianling
authors: J
authors: Xie
authors: Stanley Ho Center for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
authors: Hua
authors: H
authors: Wang
authors: School of Science and Health, The University of Western Sydney, Sydney, Australia.
authors: Chanlu
authors: C
authors: Xie
authors: School of Science and Health, The University of Western Sydney, Sydney, Australia.|Central Clinical School and Bosch Institute, The University of Sydney, Sydney, Australia.
authors: C Soon
authors: CS
authors: Lee
authors: School of Science and Health, The University of Western Sydney, Sydney, Australia.
authors: Paul
authors: P
authors: Fahey
authors: School of Science and Health, The University of Western Sydney, Sydney, Australia.|Central Clinical School and Bosch Institute, The University of Sydney, Sydney, Australia.|Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
authors: Qihan
authors: Q
authors: Dong
authors: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.|Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital/ Shanghai University of T.C.M, Shanghai, China.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, China.
authors: Hongxi
authors: H
authors: Xu
mesh_terms: D000199:Actins / Q000737:chemistry; D000328:Adult; D000368:Aged; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D029760:Garcinia / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000188:drug therapy; D010936:Plant Extracts / Q000737:chemistry*; D051304:Profilins / Q000378:metabolism*; D040901:Proteomics; D016896:Treatment Outcome
chemical_list: D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; D001577:Benzophenones; C495738:PFN1 protein, human; D010936:Plant Extracts; D051304:Profilins; C519762:guttiferone K
keywords: Guttiferone K; actin; cancer metastasis; hepatocellular carcinoma; profilin1