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Medicina (B.Aires) ; 68(1): 13-22, ene.-feb. 2008. ilus, graf, tab
Article in Spanish | LILACS | ID: lil-633509

ABSTRACT

Lonidamina (1-[ 2,4-diclorofenil metil]-1H indazol-3-ácido carboxílico), (lnd), es una droga antineoplásica cuyo mecanismo de acción se ejerce sobre el metabolismo intermedio de la glucosa. Los efectos de la lnd sobre el crecimiento celular y el metabolismo celular se investigaron en las células HT- 29, línea celular de carcinoma colónico humano, que requiere altas concentraciones de glucosa para su crecimiento indiferenciado en cultivo. La lnd en dosis de 0.2 mM disminuyó significativamente el crecimiento celular y la formación de colonias en agar; con la interrupción del tratamiento se observó el restablecimiento del crecimiento celular en 24 horas. El tratamiento con lnd produce la redistribución de los glicoconjugados y el receptor de la manosa, sin afectar en forma drástica la síntesis de glucógeno ni la de proteínas. Estas posiblemente sean las causas de la rápida reversibilidad del tratamiento.


Lonidamine (1-[ 2,4-dichlorophenyl methyl]-1H indazole-3-carboxylic acid), lnd, is an antitumoral drug acting on mitochondria and glucose metabolism. Cell growth and metabolic effects of lnd and drug post-treatment effect were investigated in undifferentiated HT-29 human colonic carcinoma cell line which requires high glucose medium concentration for growth. 0.2 mM lnd significantly decreased cell spreading and growth in monolayer or agar cell culture. After drug treatment cell growth was reestablished to control value within 24 h. Ind modified glycoconjugates and mannose-receptor distribution (analyzed by confocal microscopy), while glucose-glycogen and protein synthesis were not affected, these being the possible reasons for the fast reversible effect.


Subject(s)
Humans , Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Indazoles/therapeutic use , Apoptosis , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Gene Expression Regulation, Neoplastic/drug effects , /drug effects , Hexokinase/metabolism , Indazoles/pharmacology , Mitochondria/enzymology
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