title: DT-13 attenuates human lung cancer metastasis via regulating NMIIA activity under hypoxia condition.
abstract: Cancer metastasis plays a major role in tumor deterioration. Metastatic processes are known to be regulated by hypoxic microenvironment and non-muscle myosin IIA (NMIIA). DT-13, a bioactive saponin monomer isolated from Ophiopogon japonicus, has been reported to inhibit various cancer metastasis, but whether NMIIA is involved in the anti-metastatic activity of DT-13 under hypoxia remains to be determined. Thus, this study aims to clarify the role of DT-13 in regulating 95D cell metastasis under hypoxic microenvironment and to further investigate whether NMIIA is involved in the anti-metastatic mechanism of DT-13. We found that DT-13 significantly inhibited 95D cells metastasis in vitro and in vivo. Furthermore, hypoxia significantly inhibited the expression of NMIIA and redistributed NMIIA to the cell periphery, whereas DT-13 reversed the hypoxic effects by upregulating the expression of NMIIA. Moreover, DT-13 treatment redistributed NMIIA to the nuclear periphery and reduced the formation of F-actin in 95D cells. In addition, we found that the Raf-ERK1/2 signaling pathway is involved in regulation of NMIIA by DT-13. Collectively, these findings support NMIIA as a target of DT-13 to prevent lung cancer metastasis.
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wei
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Sen-Sen
authors.initials: SS
authors.lastname: Lin
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Ren-Ping
authors.initials: RP
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Ghulam Jilany
authors.initials: GJ
authors.lastname: Khan
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Du
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Bo-Yang
authors.initials: BY
authors.lastname: Yu
authors.affiliation: Tasly Research Institute, Tianjin Tasly Hodling Group Co., Ltd., Tianjin, P.R. China.
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Li
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Yuan
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D020409:Molecular Motor Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000199:Actins; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D012503:Saponins; C578958:ruscogenin-1-O-(glucopyranosyl-(1-2))(xylopyranosyl-(1-3))fucopyranoside; D018995:Myosin Heavy Chains