PMID- 17418595 OWN - NLM STAT- MEDLINE DCOM- 20070801 LR - 20221207 IS - 1065-6995 (Print) IS - 1065-6995 (Linking) VI - 31 IP - 9 DP - 2007 Sep TI - Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: preliminary results of an in vitro study. PG - 1069-71 AB - We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied. FAU - Ozturk, O H AU - Ozturk OH AD - Akdeniz University, Department of Biochemistry, Antalya, Turkey. FAU - Bozcuk, H AU - Bozcuk H FAU - Burgucu, D AU - Burgucu D FAU - Ekinci, D AU - Ekinci D FAU - Ozdogan, M AU - Ozdogan M FAU - Akca, S AU - Akca S FAU - Yildiz, M AU - Yildiz M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070225 PL - England TA - Cell Biol Int JT - Cell biology international JID - 9307129 RN - 0 (Antineoplastic Agents) RN - 0 (Bone Density Conservation Agents) RN - 0 (Diphosphonates) RN - 0 (Imidazoles) RN - 0W860991D6 (Deoxycytidine) RN - 6XC1PAD3KF (Zoledronic Acid) RN - Q20Q21Q62J (Cisplatin) RN - 0 (Gemcitabine) SB - IM MH - Antineoplastic Agents/pharmacology MH - Bone Density Conservation Agents/pharmacology MH - Cell Death/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cisplatin/*toxicity MH - Deoxycytidine/analogs & derivatives/pharmacology MH - Diphosphonates/*pharmacology MH - *Drug Screening Assays, Antitumor MH - Drug Synergism MH - Humans MH - Imidazoles/*pharmacology MH - Lung Neoplasms/*pathology MH - Zoledronic Acid MH - Gemcitabine EDAT- 2007/04/10 09:00 MHDA- 2007/08/02 09:00 CRDT- 2007/04/10 09:00 PHST- 2006/07/17 00:00 [received] PHST- 2007/02/01 00:00 [revised] PHST- 2007/02/18 00:00 [accepted] PHST- 2007/04/10 09:00 [pubmed] PHST- 2007/08/02 09:00 [medline] PHST- 2007/04/10 09:00 [entrez] AID - S1065-6995(07)00058-3 [pii] AID - 10.1016/j.cellbi.2007.02.004 [doi] PST - ppublish SO - Cell Biol Int. 2007 Sep;31(9):1069-71. doi: 10.1016/j.cellbi.2007.02.004. Epub 2007 Feb 25.