Marine spongian sesquiterpene phenols, dictyoceratin-C and smenospondiol, display hypoxia-selective growth inhibition against cancer cells

Bioorg Med Chem Lett. 2014 Jul 15;24(14):3155-7. doi: 10.1016/j.bmcl.2014.04.116. Epub 2014 May 9.

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.

Keywords: Cancer; Dactylospongia elegans; Dictyoceratin-C; HIF-1α; Hypoxia; Smenospondiol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Hydroxybenzoates / chemistry
  • Hydroxybenzoates / isolation & purification
  • Hydroxybenzoates / pharmacology*
  • Hypoxia / metabolism*
  • Molecular Conformation
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Phenols / chemistry
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Porifera / chemistry*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Hydroxybenzoates
  • Phenols
  • Sesquiterpenes
  • dictyoceratin-C
  • smenospondiol