title: Effects of bisphosphonates in combination with ionizing radiation and antioxidants on the growth of prostate and melanoma cells lines.
abstract: BACKGROUND
  Bisphosphonates are used in cancer-related hypercalcaemia, in complications of bone metastasis and in postmenopausal osteoporosis, and have often been associated with adverse complications.
  
  
  OBJECTIVE
  To determine the protective effect of apigenin against growth inhibition of normal epithelial human prostatic (PNT2), transgenic adenocarcinoma of mouse prostate (TRAMP-C1) and metastatic melanoma cells (B16F10) in combined treatments with bisphosphonates and ionizing radiation (IR).
  
  
  METHODS
  The growth inhibition on PNT2, TRAMP-C1 and B16F10 cells in the combined treatments with bisphosphonates (zoledronic acid, ibandronate and pamidronate) and IR in the presence and absence of apigenin was studied using a cell viability test.
  
  
  RESULTS
  Zoledronic acid had a cytotoxic effect on PNT2, TRAMP-C1 and B16F10 cells (p<0.001). However, ibandronate and pamidronate had a cytotoxic effect only on PNT2 cells (p<0.001). The administration of apigenin in combined treatment with bisphosphonates and IR showed: a decrease in the cytotoxic effect on TRAMP-C1 and B16F10 cells in the treatment with ibandronate; a protective effect on normal PNT2 and melanoma cells, but not on TRAMP-C1 cells in the treatment with zoledronic acid; and provided protection only to PNT2 cells in the treatment with pamidronate.
  
  
  CONCLUSIONS
  The use of the antioxidant produced a greater decrease in the cytotoxic effect on the non-tumor than in tumor cells when treated with bisphosphonates-alone and could be used in non-tumor pathologies. However, in a combined treatment with IR, it can also provide protection to tumor cells, thus reducing the intended effect of the IR.
authors.affiliation: Radiology and Physical Medicine Department, Faculty of Medicine/Dentistry, University of Murcia, 30100-Espinardo (Murcia), Spain. mab@um.es
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcaraz
authors.forename: Amparo
authors.initials: A
authors.lastname: Olivares
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Achel
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcaraz-Saura
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D000077268:Pamidronate; D011471:Prostatic Neoplasms / Q000473:pathology*; D011839:Radiation, Ionizing; D012878:Skin Neoplasms / Q000473:pathology*; D000077211:Zoledronic Acid
chemical_list: D000975:Antioxidants; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D047310:Apigenin; D000077268:Pamidronate; D000077557:Ibandronic Acid
keywords: B16F10 cells; PNT2; Radiation effects; TRAMP-C1; bisphosphonates; radioprotectors; radiosensitizers