Bisphosphonates decrease telomerase activity and hTERT expression in MCF-7 breast cancer cells.
Bisphosphonates are important in the management of tumours with secondary bone involvement. Recent findings have suggested that these drugs also have an effect on primary tumour burden. Telomerase is a cellular ribonucleoprotein reverse transcriptase responsible for elongation of the telomere. Telomerase expression is increased in many cancers. We studied the direct effects of clodronate, alendronate, and pamidronate (from 10(-6) to 10(-4) M) on MCF-7 human breast cancer cell line. In particular, we investigated their effect on viability, proliferation, apoptosis, human telomerase reverse transcriptase expression (h-TERT) by RT-PCR and telomerase activity. Alendronate and pamidronate showed an inhibition of viability (-63 and -35%, respectively; p < 0.0001) and proliferation of cancer cells, while no effect was observed with clodronate. Amino-bisphosphonates induced a significant increase of apoptosis in MCF-7. In addition, they showed a significant decrease in telomerase expression and activity with respect to control and to clodronate.
Dalle Carbonare
Luca
L
Department of Medical and Surgical Sciences, Clinica Medica I, University of Padova, Italy. luca.dallecarbonare@unipd.it
Valenti
Maria Teresa
MT
Azzarello
Giuseppe
G
Balducci
Elena
E
Crepaldi
Gaetano
G
Realdi
Giuseppe
G
Vinante
Orazio
O
Giannini
Sandro
S
D019386:Alendronate / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D049109:Cell Proliferation / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D000077268:Pamidronate; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004164:Diphosphonates; D004002:Clodronic Acid; C509186:TERT protein, human; D019098:Telomerase; D000077268:Pamidronate; D019386:Alendronate