title: Oridonin induces apoptosis in uveal melanoma cells by upregulation of Bim and downregulation of Fatty Acid Synthase.
abstract: Oridonin is an orally available drug isolated from Traditional Chinese Medicine. Previous studies with oridonin have demonstrated broad-spectrum anticancer activity in a variety of cancer types. However, the effect of oridonin in uveal melanoma has not been addressed. In this study, we aimed to investigate whether oridonin elicited anticancer activity and its underlying mechanism in human uveal melanoma cells. We demonstrated that oridonin potently reduced cell viability, induced apoptosis and inhibited clonogenic survival and growth with single digit micromolar concentrations in uveal melanoma OCM-1 and MUM2B cell lines. We found that oridonin markedly increased the expression of proapoptotic Bcl-2 family protein Bim in uveal melanoma cells, and knockdown Bim by small interfering RNA significantly attenuated oridonin-induced cell death, indicating an essential role of Bim in oridonin-mediated anticancer activity. Additionally, we observed that oridonin suppressed Fatty Acid Synthase (FAS) expression in uveal melanoma cells, and enforced FAS expression by insulin partially rescued the cells from oridonin-induced apoptosis, showing that inhibition of FAS also contributed to oridonin-mediated apoptosis. Taken together, we reported that oridonin displays potent anticancer effect against uveal melanoma cells through upregulation of Bim and inhibition of FAS. Since oridonin is a popular anticancer agent, our study therefore may have translational implication on the management of patients with uveal melanoma.
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Pediatric Surgery, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: xhwanggql@gmail.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ruo
authors.initials: R
authors.lastname: Qi
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yinping
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Gongquan
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: lixiaozhougz@sina.com.
authors.forename: Lixiao
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D064429:Fatty Acid Synthases / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology*; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000187:drug effects*; D014604:Uveal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D000098943:Uveal Melanoma
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D045786:Diterpenes, Kaurane; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C011959:oridonin; D064429:Fatty Acid Synthases; D020169:Caspases
keywords: Apoptosis; Bim; Fatty Acid Synthase; Oridonin; Uveal melanoma