title: Low concentrations of alendronate increase the local invasive potential of osteoblastic sarcoma cell lines via connexin 43 activation.
abstract: Bisphosphonates (BPs) are agents used for treating disorders of excessive bone resorption. In addition, due to their cell-killing activity, BPs were potent candidates for adjuvant cancer therapy. On the other hand, low-concentrations of BPs have been reported to increase cellular viability in several types of tumor cells. Therefore, we focused on the effect of BPs on cellular aggressiveness of malignant bone tumors at low concentrations. MTS assay was performed using osteosarcoma cell lines MG63 and HOS, fibrosarcoma cell line HT1080, and prostate cancer cell line PC3. All the cell lines showed toxicity at high concentrations. On the other hand, at lower concentrations, the cellular viabilities of HOS and MG63 were rather higher than those of untreated controls. Since this tendency was most evident, HOS was used for further assays, including cellular motility, bone resorption activity, and cathepsin K activity. The low-concentration of alendronate enhanced cellular viability and motility, which correlated with the expression of connexin 43 at the mRNA and protein levels. Interestingly, oleamide, a potent connexin 43 inhibitor, had an inhibitory effect on the enhanced proliferation. Our data suggest that alendronate may enhance the proliferation of osteoblastic cell line through connexin 43 activation.
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. yoshikazu543@hotmail.com
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshitani
authors.forename: Akira
authors.initials: A
authors.lastname: Kido
authors.forename: Kanya
authors.initials: K
authors.lastname: Honoki
authors.forename: Manabu
authors.initials: M
authors.lastname: Akahane
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Fujii
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy / Q000473:pathology; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009829:Oleic Acids / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D018031:Connexin 43; C500216:GJA1 protein, human; D009829:Oleic Acids; C029407:oleylamide; C534130:CTSK protein, human; D056657:Cathepsin K; D019386:Alendronate