title: Oblongifolin C inhibits metastasis by up-regulating keratin 18 and tubulins.
abstract: Tumor metastasis is the main cause of cancer-related patient death. In this study, we performed a wound healing migration screen to search for a metastatic inhibitor within our library of natural compounds. We found that oblongifolin C (OC), a natural compound extracted from Garcinia yunnanensis Hu, is an effective inhibitor of metastasis in human esophageal squamous carcinoma Eca109 cells. The transwell migration and matrigel invasion assay results also showed that OC inhibits the migration of Eca109 cells and HepG2 cells. OC can increase the expression of tubulin, indicating that OC inhibits metastasis via tubulin aggregation. In addition, the Western blotting, real-time PCR, and immunostaining results indicated that OC increases the expression of keratin18. Furthermore, the knockdown of keratin 18 by small interfering RNAs inhibited the expression of tubulin and increased the metastasis of cancer cells, suggesting that keratin 18 is the upstream signal of tubulin and plays a vital role in metastasis. A subsequent study in a tail vein injection metastasis model showed that OC can significantly inhibit pulmonary metastasis, as revealed by immunohistochemistry staining. Taken together, our results suggest that OC inhibits metastasis through the induction of the expression of keratin 18 and may be useful in cancer therapy.
authors.affiliation: 1] School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China [2] Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1] School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China [2] 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: Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, P.R. China.
authors.forename: Naihan
authors.initials: N
authors.lastname: Xu
authors.affiliation: 1] School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China [2] Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Xi
authors.affiliation: 1] School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China [2] Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Wu
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China.
authors.forename: Xiyi
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China [2] 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: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China.
authors.forename: Menghong
authors.initials: M
authors.lastname: Sun
authors.affiliation: 1] School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China [2] 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; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D029760:Garcinia / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053538:Keratin-18 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D013729:Terpenes / Q000494:pharmacology*; D014404:Tubulin / Q000096:biosynthesis*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C488421:KRT18 protein, human; D053538:Keratin-18; D010936:Plant Extracts; D034741:RNA, Small Interfering; D013729:Terpenes; D014404:Tubulin; C575447:oblongifolin C