title: Camptothecin Enhances Cell Death Induced by (177)Lu-EDTMP in Osteosarcoma Cells.
abstract: Lutetium-177 is an assured therapeutic radionuclide with favorable half-life and suitable β(-) energy. Radiolabeled (177)Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is by and large used for bone pain palliation in cancer patients. In vitro cell studies are carried out in osteosarcoma cells MG-63 to evaluate the combined effect of anticancer drug camptothecin (CPT) and (177)Lu-EDTMP. Two concentrations of (177)Lu-EDTMP (3.7 and 37 MBq) were incubated with MG63 cell line for 48 hours with and without pretreatment of CPT (10 nM) for 1 hour. After completion of incubation, the cells were harvested and cellular toxicity was estimated by LDH, MTT, and trypan blue dye. Apoptotic DNA fragmentation was estimated by ELISA kit. The expression of proteins such as bcl2, PARP, and MAPK (mitogen-activated protein kinase) that were related to apoptotic signaling pathways was assessed by western blotting. The results indicated that cellular toxicity and apoptosis were relatively higher in MG63 cells that were treated with CPT prior to treating with (177)Lu-EDTMP in comparison with the corresponding individual controls.
authors.affiliation: Isotope Applications & Radiopharmaceuticals Division, Bhabha Atomic Research Centre , Mumbai, India .
authors.forename: Chandan
authors.initials: C
authors.lastname: Kumar
authors.forename: Kusum
authors.initials: K
authors.lastname: Vats
authors.forename: Sharad P
authors.initials: SP
authors.lastname: Lohar
authors.forename: Aruna
authors.initials: A
authors.lastname: Korde
authors.forename: Grace
authors.initials: G
authors.lastname: Samuel
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D016466:CHO Cells; D002166:Camptothecin / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D003412:Cricetulus; D004357:Drug Synergism; D006801:Humans; D008187:Lutetium / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D011868:Radioisotopes / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C119503:lutetium ethylenediaminetetramethylene phosphonic acid; D008187:Lutetium; D002166:Camptothecin
keywords: 177Lu-EDTMP; apoptosis; camptothecin; cellular toxicity; osteosarcoma