Marine compounds selectively induce apoptosis in female reproductive cancer cells but not in primary-derived human reproductive granulosa cells

Mar Drugs. 2012 Jan;10(1):64-83. doi: 10.3390/md10010064. Epub 2012 Jan 10.

Abstract

Anticancer properties of tyrindoleninone and 6-bromoisatin from Dicathais orbita were tested against physiologically normal primary human granulosa cells (HGC) and reproductive cancer cell lines. Tyrindoleninone reduced cancer cell viability with IC₅₀ values of 39 µM (KGN; a tumour-derived granulosa cell line), 39 μM (JAr), and 156 μM (OVCAR-3), compared to 3516 μM in HGC. Apoptosis in HGC's occurred after 4 h at 391 µM tyrindoleninone compared to 20 µM in KGN cells. Differences in apoptosis between HGC and KGN cells were confirmed by TUNEL, with 66 and 31% apoptotic nuclei at 4 h in KGN and HGC, respectively. These marine compounds therefore have potential for development as treatments for female reproductive cancers.

Keywords: apoptosis; brominated indoles; gynaecological cancers; marine mollusc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Gastropoda / chemistry*
  • Genital Neoplasms, Female / drug therapy*
  • Genital Neoplasms, Female / pathology
  • Granulosa Cells / drug effects*
  • Homeopathy
  • Humans
  • Hydrocarbons, Brominated / pharmacology*
  • In Situ Nick-End Labeling
  • Indoles / chemistry
  • Indoles / isolation & purification
  • Indoles / pharmacology*
  • Isatin / analogs & derivatives*
  • Isatin / pharmacology
  • L-Lactate Dehydrogenase / metabolism
  • Necrosis

Substances

  • 6-bromoisatin
  • Antineoplastic Agents
  • Hydrocarbons, Brominated
  • Indoles
  • tyrindoleninone
  • Isatin
  • L-Lactate Dehydrogenase
  • Caspases