title: Apoptotic Effect of Sanggenol L via Caspase Activation and Inhibition of NF-κB Signaling in Ovarian Cancer Cells.
abstract: In the present study, the underlying apoptotic mechanism of sanggenol L was elucidated in ovarian cancer cells. Sanggenol L showed cytotoxic and antiproliferative effect in A2780, SKOV-3, and OVCAR-3 ovarian cancer cells in a concentration-dependent fashion. Consistently, sanggenol L increased sub-G1 phase population and early and late apoptotic portion in ovarian cancer cells. Also, sanggenol L activated caspase9/3, suppressed the phosphorylation of IκBα and p65 NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), attenuated the expression of Cyclin D1, and cleaved poly(adenosine diphosphate ribose -ribose) polymerase in SKOV-3, A2780, and OVCAR-3 cells. Furthermore, sanggenol L blocked nuclear translocation of NF-κB and also attenuated the expression of NF-κB related genes such as c-Myc, Cyclin D1, and Bcl-X L, Bcl-2, in lipopolysaccharide-treated SKOV-3 cells. Overall, our findings for the first time suggest that sanggenol L induces apoptosis via caspase activation and inhibition of NF-κB/IκBα phosphorylation as a potent chemotherapeutic agent for ovarian cancers.
authors.affiliation: Department of East West Medical Science, Graduate School of East West Medical Science, Kyung Hee University, Yongin, 446-701, Korea.
authors.forename: Moon Sik
authors.initials: MS
authors.lastname: Nam
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Deok-Beom
authors.initials: DB
authors.lastname: Jung
authors.affiliation: Department of Oriental Medicine Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
authors.forename: Kyeong-Hwa
authors.initials: KH
authors.lastname: Seo
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Bo-Im
authors.initials: BI
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Ju-Ha
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Chosun Nursing College, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Korea.
authors.forename: Jung Hyo
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Oriental Medicine Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin, 446-701, Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D031625:Morus / Q000737:chemistry; D000072000:NF-KappaB Inhibitor alpha; D010051:Ovarian Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C000595707:BCL2 protein, human; C530104:CCND1 protein, human; D044950:Flavanones; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051020:bcl-X Protein; C000608444:sanggenol L; D019938:Cyclin D1; D000072000:NF-KappaB Inhibitor alpha; D020169:Caspases
keywords: NF-κB; PARP; apoptosis; caspase 9/3; ovarian cancer cells; sanggenol L