Bisphosphonates induce apoptosis in CLL cells independently of MDR phenotype.
OBJECTIVE
The anti-tumoral activity of bisphosphonates (BPs) has been reported in leukemia. In this study, we attempted to evaluate the apoptotic effects of the BPs pamidronate (PAM) and zoledronic acid (ZOL) in chronic lymphocytic leukemia (CLL) samples, and to correlate it with clinical parameters and multidrug resistance (MDR) phenotype (P-glycoprotein and multidrug resistance-related protein expression and/or their functional activity).


RESULTS
Both BPs were able to induce apoptosis significantly. No correlation was observed between BP-induced apoptosis and clinical parameters or MDR phenotype.


CONCLUSIONS
Our data suggest that concurrent or sequential administration of BPs with conventional chemotherapeutic drugs may have significant therapeutic potential for CLL patients.
Silva
Karina Lani
KL
Laboratório de Hematologia Celular e Molecular, Serviço de Hematologia, Hospital do Câncer I, Instituto Nacional de Câncer, Praça Cruz Vermelha 23, 6 andar, Centro, Rio de Janeiro, RJ, CEP. 20230-130, Brazil.
Vasconcellos
Deborah Vidal
DV
Castro
Eric Delfraro de Paula
ED
Vasconcelos
Flavia da Cunha
FC
Bigni
Ricardo
R
Maia
Raquel Ciuvalschi
RC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000077268:Pamidronate; D010641:Phenotype; D000077211:Zoledronic Acid
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077268:Pamidronate