Zoledronic acid induces caspase-dependent apoptosis in renal cancer cell lines.
OBJECTIVE
To study and characterize the potential antitumoral effects of zoledronic acid (ZA) on renal cancer cell lines in vitro.


METHODS
Three different and well-characterized renal cancer cell lines were studied, namely ACHN, A-498 and CAKI-2. The cytotoxic potential of ZA was evaluated using a fluorometric microculture cytotoxic assay. The degree of M30 induction following ZA treatment was measured using an M30 enzyme-linked immunosorbent assay (ELISA), and the 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 three cell lines following treatment with ZA, compared with untreated controls. This effect was most pronounced for the ACHN cells, as only 4% were viable following incubation with ZA for 72 h. 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.


CONCLUSIONS
ZA exerts cytotoxic effects on renal cancer cell lines in vitro. These include caspase-dependent induction of apoptosis, which can be quantified and visualized using M30 ELISA and immunofluorescence, respectively. The clinical relevance of this finding needs to be further investigated, but these results indicate that ZA may be a treatment alternative for selected patients with skeletal metastasized renal cell cancer, particularly for those with impaired performance status without other treatment options.
Ullen
Anders
A
Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden. anders.ullen@karolinska.se
Schwarz
Stephan
S
Lennartsson
Lena
L
Kalkner
Karl-Mikael
KM
Sandstrom
Per
P
Costa
Fernanda
F
Lennernas
Bo
B
Linder
Stig
S
Nilsson
Sten
S
D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000502:physiology; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay; D005470:Fluorometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D020169:Caspases