RESUMO
BACKGROUND: The role of mitochondrial DNA (mtDNA) in anthracycline-induced apoptosis is controversial. Sabarubicin accumulates in the mitochondria of A2780 human ovarian tumor cells. The effects of this new anthracycline on the structure and the functionality of mtDNA, as well as on the apoptosis of mtDNA-depleted cells have been investigated. MATERIALS AND METHODS: Sabarubicin-induced mtDNA cleavage was detected by Southern blotting and mitochondrial mRNA expression was analyzed by real-time PCR. Apoptosis was studied in mtDNA-depleted (theta0) and parental (theta+) A2780 cells detecting nuclear DNA fragmentation using ELISA and cytofluorimetrically using Annexin V/PI staining. Mitochondrial membrane potential was studied using the cyanine dye JC-1. RESULTS: Sabarubicin induced mtDNA cleavage in the A2780 cells, but this damage did not affect mitochondrial mRNA expression. Apoptosis was induced by sabarubicin in theta0 as well as in theta+ cells. CONCLUSION: The results showed that mtDNA did not influence anthracycline-induced apoptosis in A2780 cells.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , DNA Mitocondrial/metabolismo , Dissacarídeos/farmacologia , Doxorrubicina/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Antibióticos Antineoplásicos/farmacocinética , Apoptose/genética , Southern Blotting , Linhagem Celular Tumoral , Dissacarídeos/farmacocinética , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In the search for new strategies against HIV-1 and on the basis of a number of previous studies reporting on the capacity of certain polyanionic compounds to influence the replication of HIV-1, we prepared a few chemically oversulfated dermatan and chondroitin sulfates. Four of these compounds and two samples of heparin were bound to activated Sepharose through either their carboxylic groups, or their aldehydic groups, or their deacetylated primary amino groups. Some of these so-derivatised resins, packed into columns, proved able to remove HIV-1 IIIB, a laboratory adapted strain, and one clinical primary isolate from an AIDS patient, from infected cell culture medium. The resins bind the virus very tightly and could be useful for capturing the virus from infected fluids.