Naslov
In vitro activity of dimethylarsinic acid against human leukaemia and multiple myeloma cell lines

Autori
Duzkale, H. ; Jilani, I. ; Oršolić, Nada ; Zingaro, R.A. ; Golemović, Mirna ; Giles, F. ; Kantarjian, H. ; Albitar, M. ; Freireich, E.J. ; Verstovšek, Srđan

Izvornik
Cancer chematotherapy and pharmacology (0344-5704) 51 (2003), 5; 427-432

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

Ključne riječi
Dimethylarsinic acid; Arsenic trioxide

Sažetak
Arsenic trioxide (As2O3), an inorganic arsenic compound, has recently been approved for the treatment of relapsed or refractory acute promyelocytic leukemia. However, systemic toxicity associated with As2O3 treatment remains a problem. Inorganic arsenic is detoxified in vivo by methylation reactions into organic arsenic compounds that are less toxic. Methods and results: We investigated the antiproliferative and cytotoxic activity of dimethylarsinic acid(DMAA), an organic arsenic derivative and major metabolic by-product of As2O3, against a panel of eight leukemia and multiple myeloma cell lines. As2O3 was tested in comparison. In clonogenic assay, the average concentration of DMAA that suppressed cell colony growth by 50% was 0.5 - 1 mM, while for As2O3 it was on average 1 - 2 lM. At those concentrations DMAA and As2O3 had significantly less e.ect on colony growth of normal progenitor cells. Cytotoxic doses of DMAA and As2O3 in 3-day trypan blue dye exclusion assay experiments were similar to doses efective in clonogenic assay. Assessment of apoptosis by annexin V assay revealed a high rate of apoptosis in all cell lines treated with DMAA and As2O3, but signi.cantly less efect on normal progenitor cells. DMAA, unlike As2O3, had no efect on the maturation of leukemic cells. Conclusions: DMAA exerts diferential antiproliferative and cytotoxic activity against leukemia and multiple myeloma cells, with no significant efect on normal progenitor cells. However, concentrations of DMAA needed to achieve such efficacy are up to 1000 times those of As2O3. Evaluation of novel organic arsenic that would combine the high efficacy of As2O3 and the low toxicity of DMAA is warranted.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA