title: Resveratrol attenuates norepinephrine-induced ovarian cancer invasiveness through downregulating hTERT expression.
abstract: Stress hormone norepinephrine (NE) has been associated with acquisition of cancer progression, and naturally occurring phytoalexin resveratrol (REV) has been known to suppress cancer growth and progression. In the present study, we determine the effect of REV on NE-induced ovarian cancer invasiveness. Pretreatment of REV significantly inhibited NE-induced ovarian cancer cell epithelial-to-mesenchymal transition with concomitant recovery of E-cadherin expression. In addition, our data showed that REV downregulates NE-induced human telomerase reverse transcriptase (hTERT) expression through inhibiting Src phosphorylation and HIF-1α expression. Further, REV reduced NE-induced Slug expression and subsequent ovarian cancer invasion. More importantly, combined treatment of REV with a pharmacological inhibitor of beta adrenergic receptor significantly attenuated NE-induced ovarian cancer invasion compared to single treatment. Therefore, we demonstrate interference of a Src and HIF-1α/hTERT/Slug signaling cascade by REV, providing potential therapeutic targets and inhibition of ovarian cancer.
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors.forename: Seung Hwa
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors.forename: Yu Na
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-747, Republic of Korea.
authors.forename: Chang Gyo
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Daejeon Regional Cancer Center, College of Medicine, Chungnam National University, 821 Medical Science Bldg., 681 Gasuwon-dong, Seo-gu, Daejeon, 302-718, Republic of Korea. gmhur@cnu.ac.kr.
authors.forename: Gang Min
authors.initials: GM
authors.lastname: Hur
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, 6 Munhwa-dong, Jung-gu, Daejeon, 301-747, Republic of Korea. hoi@konyang.ac.kr.
authors.forename: Hoi Young
authors.initials: HY
authors.lastname: Lee
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009638:Norepinephrine / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D013267:Stilbenes; D019061:src-Family Kinases; C509186:TERT protein, human; D019098:Telomerase; D000077185:Resveratrol; D009638:Norepinephrine
keywords: Metastasis; Ovarian cancer; Resveratrol; Telomerase