Bisphosphonates, specifically Zometa, is commonly used in the treatment of men with advanced prostate cancer. Zometa is used to treat and protect bones from developing fractures.
Bisphosphonates are potent inhibitors of bone resorption. Additionally, in vitro studies show that zolendronic acid also inhibits prostate cancer cell growth by activating apoptosis (A form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area). investigated
Researchers from the Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital in Taipei, Twian investigated whether zolendronic acid also inhibits prostate cancer cell growth by autophagy (another type of planned cell death which involves the process of self-digestion by a cell through the action of enzymes originating within the same cell). They studied the induction of autophagy in the PC-3, DU-145, LNCaP and CRW22Rv1 prostate cancer cell lines upon zolendronic acid treatment.
LC3-II protein formation was detected by Western blot. LC3-II incorporation into autophagosomes was detected by immunofluorescence staining. Acidic organelle formation was detected by acridine orange staining. Rescue experiments using an apoptosis inhibitor and/or an autophagy inhibitor were performed by MTT assay.
Autophagy induction was detected by formation of the LC3-II protein after exposure to 100 ?M zolendronic acid. LC3-II and caspase-3 processing was detected 6 days after treatment. Acidic organelles were detectable by acridine orange staining and immunofluorescence showed round-up and condensed staining of LC3-II, suggesting autophagosome formation in the cytoplasm during autophagic cell death.
Cell growth was rescued only by administering an apoptosis and autophagy inhibitor during zolendronic acid treatment, indicating that zolendronic acid induces prostate cancer death by both apoptotic and autophagic cell death.
This study might be the first study showing that zolendronic acid markedly inhibits human prostate cancer cell growth through autophagic cell death. Besides providing positive effects on bones, Zolendronic acid shows anticancer activity via apoptosis and autophagy. These findings can potentially contribute to the beneficial use of zolendronic acid for prostate cancer treatment.
Reference: J Urol. 2011 Feb 18. Epub ahead of print.
doi: 10.1016/j.juro.2010.11.045; Lin JF, Lin YC, Lin YH, Tsai TF, Chou KY, Chen HE, Hwang TI.
Joel T Nowak, M.A., M.S.W.