Zoledronic acid decreases mRNA six-transmembrane epithelial antigen of prostate protein expression in prostate cancer cells.
BACKGROUND
Zoledronic acid (Zol) is used successfully to inhibit bone resorption in tumor bone disease of various human cancer. Zol inhibits the mevalonate pathway and other potential targets include the inhibition of tyrosine phosphatase activity, disruption of metalloproteinase, secretion and down-regulation of the catalytic subunit of telomerase (hTERT). The six-transmembrane epithelial antigen of prostate protein (STEAP) is a new marker highly expressed at all phases of prostate cancer.


OBJECTIVE
Here, we analyzed for the first time the effect of Zol on STEAP gene expression in prostate cancer cells.


METHODS
We evaluated the effects of Zol in STEAP gene expression by RT real time PCR in androgen-sensitive (LNCaP) and androgen-non-sensitive (PC3 and DU145) cell lines. To confirm the pro-apoptotic effect of Zol, we also analyzed the caspase-3 gene expression, that resulted up-regulated in cancer cell apoptosis.


RESULTS
Zol strongly decreased cell viability and lowered STEAP gene expression in a dose-dependent manner. In addition, this effect was accompanied by an increase of apoptotic index and an up-regulation of caspase-3 gene expression.


CONCLUSIONS
Zol may affect cancer cells also by targeting the gene expression of STEAP.
Valenti
M T
MT
Department of Biomedical and Surgical Sciences, Clinic of Internal Medicine D, University of Verona, 37134 Verona, Italy.
Giannini
S
S
Donatelli
L
L
Realdi
G
G
Lo Cascio
V
V
Dalle Carbonare
L
L
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D000077211:Zoledronic Acid
D000951:Antigens, Neoplasm; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D012333:RNA, Messenger; D000077211:Zoledronic Acid; D010088:Oxidoreductases; C432763:STEAP1 protein, human; D053148:Caspase 3