title: Zoledronic acid exerts antitumor effects in NB4 acute promyelocytic leukemia cells by inducing apoptosis and S phase arrest.
abstract: The aim of this study was to investigate the antitumor effect of zoledronic acid (ZOL) in the NB4 human acute promyelocytic leukemia (APL) cell line and explore the potential mechanism of action of this compound. NB4 cells were exposed to various concentrations (0-200μM) of ZOL. Cell viability was measured by MTS assay. The extent of cell apoptosis and distribution of cells in the different phases of the cell cycle were analyzed with flow cytometry. The expression of apoptosis- and cell cycle-related proteins was assayed by Western blot. The combined effect of ZOL and arsenic trioxide (ATO) on the proliferation of NB4 cells was also determined. The results of this study indicate that ZOL inhibits cell proliferation in a time- and dose-dependent fashion and also induces apoptosis and S phase arrest in a dose-dependent manner. The Western blot analysis confirmed the induction of apoptosis and S phase arrest, revealing that the pro-apoptosis proteins Bax, Puma and activated caspase-9 were upregulated and the anti-apoptosis proteins Bcl-2 and Bcl-xL were downregulated. ZOL at a concentration of 50μM synergized with 0.5μM ATO on the growth inhibition of NB4 cells. Taken together, our data indicate that ZOL exerts a potent antitumor effect on NB4 cells by inducing apoptosis and cell cycle arrest, and that ZOL can synergize with the traditional chemotherapy drug ATO.
authors.affiliation: Department of Hematology, First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, 510080 Guangzhou, PR China.
authors.forename: Shou-Sheng
authors.initials: SS
authors.lastname: Liu
authors.affiliation: Department of Pathology, Guangzhou First People's Hospital, No. 1 Panfu Road, 510080 Guangzhou, PR China.
authors.forename: Xiao-Pai
authors.initials: XP
authors.lastname: Wang
authors.affiliation: Department of State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre of Sun Yat-sen University, No. 54 Martyrs South Road, 510080 Guangzhou, PR China.
authors.forename: Xiu-Bo
authors.initials: XB
authors.lastname: Li
authors.affiliation: Department of Oncology, Guangdong General Hospital, No. 106 Zhongshan Second Road, 510080 Guangzhou, PR China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Liang
authors.affiliation: Department of Hematology, Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510080 Guangzhou, PR China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Department of Hematology, Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, 510080 Guangzhou, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pathology, Medical College of Jinan University, No. 601 Whampoa, Road West, 510080 Guangzhou, PR China.
authors.forename: Xue-Yun
authors.initials: XY
authors.lastname: Zhong
authors.affiliation: Department of Hematology, First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Second Road, 510080 Guangzhou, PR China. Electronic address: cyx1228@21cn.com.
authors.forename: Yun-Xian
authors.initials: YX
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000502:physiology; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D016196:S Phase / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Apoptosis; Arsenic trioxide; Cell cycle; NB4 cells; Zoledronic acid