title: Moscatilin inhibits epithelial-to-mesenchymal transition and sensitizes anoikis in human lung cancer H460 cells.
abstract: Metastasis in lung cancer has been recognized as an important cause of high mortality. Resistance to anoikis and the epithelial-to-mesenchymal transition (EMT) are critical factors for the successful spread of cancer cells. Compounds that suppress these features of cancer cells should be potentially active for anti-metastasis approaches. We have demonstrated for the first time that moscatilin, at its non-toxic concentrations to lung cancer cells and human normal keratinocytes, significantly decreases lung cancer cell survival in the detached condition, and suppresses the formation of tumors in an anchorage-independent growth assay. Furthermore, we found that moscatilin significantly decreased the activated level of survival proteins, namely ERK and Akt. In addition, moscatilin down-regulated cavelolin-1 (Cav-1), leading to a reduction in anti-apoptotic Mcl-1 protein. In terms of EMT, treatment of the cells with moscatilin significantly suppressed mesenchymal cell markers, namely vimentin, Slug, and Snail. These results indicate that moscatilin inhibited anoikis resistance in lung cancer cells via survival suppression, Cav-1 down-regulation, and inhibition of EMT. The compound could therefore be beneficial for the treatment and prevention of lung cancer metastasis.
authors.affiliation: Faculty of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand.
authors.forename: Kesarin
authors.initials: K
authors.lastname: Busaranon
authors.affiliation: Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Preeyaporn
authors.initials: P
authors.lastname: Plaimee
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Boonchoo
authors.initials: B
authors.lastname: Sritularak
authors.affiliation: Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand. pithi.c@chula.ac.th.|Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand. pithi.c@chula.ac.th.
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D023102:Anoikis / Q000187:drug effects*; D001593:Benzyl Compounds / Q000494:pharmacology*; D051242:Caveolin 1 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009362:Neoplasm Metastasis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis*
chemical_list: D001593:Benzyl Compounds; D051242:Caveolin 1; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; C071845:dendrophenol
keywords: Anchorage-independent growth; Anoikis; Epithelial-to-mesenchymal transition (EMT); Lung cancer; Metastasis; Moscatilin