Zoledronic acid exerts antitumor effects in NB4 acute promyelocytic leukemia cells by inducing apoptosis and S phase arrest

• Published in: Biomedicine & pharmacotherapy Vol. 68; no. 8; pp. 1031 - 1036
• Main Authors: Liu, Shou-Sheng, Wang, Xiao-Pai, Li, Xiu-Bo, Liang, Jia-Yi, Liu, Ling-Ling, Lu, Ying, Zhong, Xue-Yun, Chen, Yun-Xian
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2014
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Arsenic trioxide; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - physiology; Diphosphonates - pharmacology; Diphosphonates - therapeutic use; Dose-Response Relationship, Drug; Humans; Imidazoles - pharmacology; Imidazoles - therapeutic use; Internal Medicine; Leukemia, Promyelocytic, Acute - drug therapy; Medical Education; NB4 cells; S Phase - drug effects; S Phase - physiology; Treatment Outcome; Zoledronic acid; Zoledronic acid; NB4 cells; Arsenic trioxide; Cell cycle; Apoptosis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2014.09.004

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 (0–200 μM) 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 50 μM synergized with 0.5 μM 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.