title: Protein kinase Cα-mediated cytotoxic activity of ineupatorolide B from Inula cappa DC. in HeLa cells.
abstract: There is an ongoing search for plant-derived sesquiterpenes, particularly for those with anticancer activity against human cancer cells. The sesquiterpene ineupatorolide B (InB), isolated from the Inula cappa, showed potent growth-inhibitory activity against HeLa cells but less activity against MM1-CB melanoma cells. Staining by terminal deoxynucleotidyl transferase dUTP nick-end labeling method revealed that this activity was, at least in part, due to the induction of apoptosis. The activities of major transcription factors were examined by using a luciferase reporter assay. The results showed that the transactivation ability of nuclear factor of activated T-cell (NFAT) was enhanced. The activation of NFAT by InB was largely suppressed by preincubation with protein kinase C (PKC) inhibitors such as staurosporine and K252a. Western blot analysis revealed that the the levels of phosphorylated PKCα, but not other subtypes, increased after treatment with InB. Knockdown of PKCα using siRNA attenuated the cytotoxic activity of InB. Thus, InB may exhibit growth-inhibitory activity through the activation of PKCα, followed by an increase in NFAT transactivation ability.
authors.affiliation: Department of Forensic Medicine, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
authors.affiliation: Department of Forensic Medicine, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cong
authors.affiliation: Department of Forensic Medicine, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Qing-Wen
authors.initials: QW
authors.lastname: Shi
authors.affiliation: Department of Forensic Medicine, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
authors.forename: Si-Ming
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kita
authors.affiliation: Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sugaya
authors.affiliation: Department of Environmental Biochemistry, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D038143:Inula / Q000737:chemistry; D050778:NFATC Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering; D012717:Sesquiterpenes / Q000008:administration & dosage*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D050778:NFATC Transcription Factors; D034741:RNA, Small Interfering; D012717:Sesquiterpenes; D051571:Protein Kinase C-alpha