The effect of gossypol and 6-aminonicotinamide on tumor cell metabolism: a 31P-magnetic resonance spectroscopic study.
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.
Keniry
M A
MA
Research School of Chemistry, Australian National University, Canberra A.C.T.
Hollander
C
C
Benz
C C
CC
D015120:6-Aminonicotinamide / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide; D009711:Nucleotides / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010758:Phosphorus; D013403:Sugar Phosphates / Q000378:metabolism
D009711:Nucleotides; D010710:Phosphates; D010743:Phospholipids; D013403:Sugar Phosphates; D009536:Niacinamide; D010758:Phosphorus; D015120:6-Aminonicotinamide; D006072:Gossypol