Inhibitory effect of vanillin-like compounds on respiration and growth of adenocarcinoma TA3 and its multiresistant variant TA3-MTX-R.
The effects of some imine and amine derivatives of vanillin on the respiration rate of mouse mammary adenocarcinoma TA3 line, its multiresistant variant TA3-MTX-R line and mouse hepatocytes, together with their respective mitochondrial fractions, are described. These derivatives inhibit respiration in both tumour cell lines more effectively than vanillin in the absence or presence of the uncoupler CCCP. Since both types of derivatives block the electron flow, mainly through the NADH-CoQ span, they behave as oxidative phosphorylation inhibitors. Thus, they prevent ATP synthesis and alter cellular processes requiring energy, which would lead to cellular death. Amine derivatives of vanillin present a similar effect on both tumour cell lines, being amine C the most efficient inhibitor. Moreover, mouse hepatocytes are about 4-fold less sensitive to amine C than tumour cells. These amine derivatives are better inhibitors than the corresponding imines; probably because they should interact better with the respiratory chain reaction site.
Department of Organic and Physical Chemistry, Faculty of Chemical and Pharmaceutical Sciences, PO Box 233, Olivos 1007, -7, Santiago, Chile. gcordano@ciq.uchile.cl
Gianni
G
Cordano
Jacqueline
J
Pezoa
Sergio
S
Muñoz
Enrique
E
Rivera
Jorge
J
Medina
Luis J
LJ
Núñez-Vergara
Mario
M
Pavani
Aníbal
A
Guerrero
Jorge
J
Ferreira
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D022781:Hepatocytes / Q000378:metabolism; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014475:Uncoupling Agents / Q000494:pharmacology
D000970:Antineoplastic Agents; D001547:Benzaldehydes; D014475:Uncoupling Agents; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C100058:vanillin