Inhibitory effect of nordihydroguaiaretic acid and its tetra-acetylated derivative on repiration and growth of adenocarcinoma TA3 and its multiresistant variant TA3MTX-R

Plaza C.; Pavani, M.; Faundez, M; Maya J.D.; Morello A.; Ferreira J.; Cumsille M.A.; Becker, M.I; De Ioannes, A.

Keywords: acid, electron, oxygen, inhibition, transport, resistance, mouse, survival, animals, culture, proliferation, cell, liver, transplantation, efficacy, cancer, mice, metabolism, tumor, experiment, consumption, adenocarcinoma, male, acetylation, cisplatin, doxorubicin, cyanide, multiple, respiration, drug, adenosine, article, carbonyl, fluorouracil, breast, mitochondrial, neoplasm, potency, controlled, animal, study, multidrug, derivative, Rate, nonhuman, triphosphate, Resistance,, glutamic, vinblastine, Mitochondria,, Line,, mitoxantrone, malic, Ubiquinone, chlorophenylhydrazone, nordihydroguaiaretic, duroquinol, tetracetylated

Abstract

The effects of nordihydroguaiaretic acid (NDGA) and its tetraacetylated derivative (NDGATA) on the growth, oxygen consumption, adenosine 5′-triphosphate (ATP) level and viability of mouse mammary adenocarcinoma TA3 and its multiresistant variant TA3-MTX-R cell lines were determined. NDGA inhibited mitochondrial carbonyl cyanide m-chlorophenylhydrazone (CCCP)-stimulated oxygen consumption in mouse liver and tumor cells when glutanuite plus malate or succinate was added as substrate. The effects were considerably weaker when respiration was supported by duroquinol, indicating that NDGA inhibited primarily mitochondrial electron flow located at some point before ubiquinone. Although NDGATA only inhibited the electron flaw:through complex I, it was more efficient and selective than NDGA because mouse liver mitochondria were significantly less sensitive to it than both tumor cell lines tested. NDGA and NDGATA inhibited mitochondrial ATP synthesis and, consequently, cell viability and growth rate were also decreased. NDGA and NDGATA inhibited the growth of intramuscularly implanted tumor cells, indicating that NDGATA was also antineoplastic in vivo. In conclusion, NDGATA is cytotoxic to tumor cells, provoking selective induction of mitochondrial dysfunctions, which could be interesting as potential antitumoral agent.

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Título según SCOPUS: Inhibitory effect of nordihydroguaiaretic acid and its tetra-acetylated derivative on repiration and growth of adenocarcinoma TA3 and its multiresistant variant TA3MTX-R
Título de la Revista: IN VIVO
Volumen: 22
Número: 3
Editorial: INT INST ANTICANCER RESEARCH
Fecha de publicación: 2008
Página de inicio: 353
Página final: 362
Idioma: eng
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-45949100666&partnerID=q2rCbXpz
Notas: SCOPUS