The effect of gossypol and 6-aminonicotinamide on tumor cell metabolism: a 31P-magnetic resonance spectroscopic study

Biochem Biophys Res Commun. 1989 Oct 31;164(2):947-53. doi: 10.1016/0006-291x(89)91550-7.

Abstract

31P-Magnetic resonance spectroscopy has been used to assess the changes in the levels of water-soluble phosphate pools in T47-D breast carcinoma cells induced by the antimitochondrial drugs, gossypol and 6-aminonicotinamide. A decrease in the NTP/Pi ratio occurred after treatment with gossypol. No change in the NTP/Pi ratio occurred on treatment with 6-aminonicotinamide; however, a substantial accumulation of 6-phosphogluconate was observed. Pretreatment of T47-D cells with gossypol prevented the accumulation of 6-phosphogluconate. This facile and non-invasive approach suggests that the oxidative part of the pentose-phosphate shuttle is an important source of reducing equivalents in T47-D cells. This pathway may prove to be a useful target for site-directed drug attack in carcinoma cell lines that require large quantities of NADP for the synthesis of fatty acids and steroids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 6-Aminonicotinamide / pharmacology*
  • Breast Neoplasms / metabolism*
  • Cell Line
  • Female
  • Gossypol / pharmacology*
  • Humans
  • Magnetic Resonance Spectroscopy / methods
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Niacinamide
  • Nucleotides / metabolism*
  • Phosphates / metabolism
  • Phospholipids / metabolism
  • Phosphorus
  • Sugar Phosphates / metabolism

Substances

  • Nucleotides
  • Phosphates
  • Phospholipids
  • Sugar Phosphates
  • Niacinamide
  • Phosphorus
  • 6-Aminonicotinamide
  • Gossypol