title: Marine spongian sesquiterpene phenols, dictyoceratin-C and smenospondiol, display hypoxia-selective growth inhibition against cancer cells.
abstract: In the course of our search for hypoxia-selective growth inhibitors against cancer cells, a sesquiterpene phenol, dictyoceratin-C (1), was isolated from the Indonesian marine sponge of Dactylospongia elegans under the guidance of the constructed bioassay. Dictyoceratin-C (1) inhibited proliferation of human prostate cancer DU145 cells selectively under hypoxic condition in a dose-dependent manner at the concentrations ranging from 1.0 to 10 μM. The subsequent structure-activity relationship study using nine sesquiterpene phenol/quinones (2-10), which were isolated from marine sponge, was executed. We found that smenospondiol (2) also exhibited the similar hypoxia-selective growth inhibitory activity against DU145 cells, and the para-hydroxybenzoyl ester moiety would be important for hypoxia-selective growth inhibitory activity of 1. In addition, the mechanistic analysis of dictyoceratin-C (1) revealed that the 10 μM of 1 inhibited accumulation of Hypoxia-Inducible Factor-1α under hypoxic condition.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan. Electronic address: araim@phs.osaka-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawachi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Chemistry, Faculty of Science, Lampung University, Jl. Prof. Dr. Sumantri Brodjonegoro No. 1, Bandar Lampung 35145, Indonesia.
authors.forename: Andi
authors.initials: A
authors.lastname: Setiawan
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan. Electronic address: kobayasi@phs.osaka-u.ac.jp.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D062385:Hydroxybenzoates; D010636:Phenols; D012717:Sesquiterpenes; C493697:dictyoceratin-C; C000595511:smenospondiol
keywords: Cancer; Dactylospongia elegans; Dictyoceratin-C; HIF-1α; Hypoxia; Smenospondiol