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Zoledronic acid induces caspase-dependent apoptosis in renal cancer cell lines
Scandinavian Journal of Urology and Nephrology, 12/22/08

Ullen A et al. - In a study to assess and characterize the potential antitumoral effects of zoledronic acid (ZA) on renal cancer cell lines in vitro, it seems that ZA exerts cytotoxic effects on renal cancer cell lines in vitro, including caspase-dependent induction of apoptosis. ZA may be a treatment alternative for selected pts with skeletal metastasized renal cell cancer, particularly for those with impaired performance status without other treatment options.

Methods

3 different and well-characterized renal cancer cell lines were studied, namely ACHN, A-498 and CAKI-2.
Cytotoxic potential of ZA was evaluated using a fluorometric microculture cytotoxic assay.
Degree of M30 induction following ZA treatment was measured using an M30 enzyme-linked immunosorbent assay, and blockage of this effect was studied using a pan-caspase inhibitor.
Immunofluorescence of the M30 neoepitope was performed to visualize the M30-inducing properties of ZA.

Results

A significant reduction in viable cells was seen for all 3 cell lines following treatment with ZA vs untreated controls.
This effect was most pronounced for the ACHN cells, as only 4% were viable following incubation with ZA for 72h.
A concomitant increase in the apoptosis significant caspase-dependent M30 antigen was demonstrated; this effect could be blocked by the pan-caspase inhibitor Z-VAD.

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