Naslov
Inhibition of apoptosis is the cause of resistance to doxorubicin in human breast adenocarcinoma cells

Autori
Osmak, Maja ; Brozović, Anamaria ; Ambriović-Ristov, Andreja ; Hadžija, Mirko ; Pivčević, Branka ; Smital, Tvrtko

Izvornik
Neoplasma (0028-2685) 45 (1998), 4; 223-230

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
drug resistance ; doxorubicin ; breast adenocarcinoma cells ; apoptosis

Sažetak
In our previous paper we have described the isolation and characterisation of a doxorubicin ( DOX ) resistance subline of breast adenocarcinoma SC6 cells. These cells were obtained after the treatment with low, clinicaly relevant doses of doxorubicin. They became cross-resistant to different wide used cytostatics. The expression of several genes involved in mitotic signal transduction, as well as cathepsins D and L, was similar in both parental and doxorubicin treated cells. The aim of this study was examine the molecular mechanisms involved in resistance of these cells to doxorubicin. Activity of plasma membrane Pgp was examined in parental and resistant cells due to rhodamine-accumulation assay. The involvement of glutahione ( GSH ) and glutathione S-transferase ( GST ) in resistance to doxorubicin was determined in MTT modified assay due to the addition of specific inhibitors: buthionine sulfoximine ( for GSH ) or ethacrynic acid ( for GST ). The kinetic of apoptosis was confirmed by analysing DNA fragmentation in agarose gel. Our results indicate that P-glycoprotein, glutathion or glutathione transferase were involved in resistance of SC6 cells to doxorubicin. However, the apoptosis was inhibited in doxorubicin-resistant cells. Therefore, even low doses of doxorubicin can induce the resistance to this drug due to inhibition of apoptosis.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA