BACKGROUND: Bisphosphonates are widely used for the treatment and prevention of osteoporosis and are also effective in the treatment of bone metastasis of prostate cancer. Several mechanisms underlying the antitumor effect of bisphosphonates have been proposed, including direct effects on tumor cells, such as induction of apoptosis and inhibition of invasion. MATERIALS AND METHODS: The detached and adherent cells after incadronate treatment were collected separately and stained with trypan blue solution. RESULTS: It was found that incadronate induced cell detachment with dephosphorylation of focal adhesion kinase (FAK). The induction of cell detachment by incadronate was prevented by coincubation with geranylgeraniol. The activation of caspase-3 was observed in incadronate-treated floating cells, but not in the adherent cells. A caspase inhibitor did not inhibit cell detachment by incadronate but it markedly prevented cell death. CONCLUSION: These results suggest that incadronate induces cell detachment, followed by caspase-dependent apoptosis.
BACKGROUND:Bisphosphonates are widely used for the treatment and prevention of osteoporosis and are also effective in the treatment of bone metastasis of prostate cancer. Several mechanisms underlying the antitumor effect of bisphosphonates have been proposed, including direct effects on tumor cells, such as induction of apoptosis and inhibition of invasion. MATERIALS AND METHODS: The detached and adherent cells after incadronate treatment were collected separately and stained with trypan blue solution. RESULTS: It was found that incadronate induced cell detachment with dephosphorylation of focal adhesion kinase (FAK). The induction of cell detachment by incadronate was prevented by coincubation with geranylgeraniol. The activation of caspase-3 was observed in incadronate-treated floating cells, but not in the adherent cells. A caspase inhibitor did not inhibit cell detachment by incadronate but it markedly prevented cell death. CONCLUSION: These results suggest that incadronate induces cell detachment, followed by caspase-dependent apoptosis.
Authors: Sanna S Virtanen; Tamiko Ishizu; Jouko A Sandholm; Eliisa Löyttyniemi; H Kalervo Väänänen; Johanna M Tuomela; Pirkko L Härkönen Journal: Oncotarget Date: 2018-08-24