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Article

Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition

  • Authors:
    • Tai Yang
    • Min-Hui Li
    • Jin Liu
    • Ning Huang
    • Ning Li
    • Si‑Nian Liu
    • Yang Liu
    • Tao Zhang
    • Qiang Zou
    • Hua Li
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, Chengdu Medical College, Chengdu, Sichuan 610083, P.R. China, Department of Oncology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China
  • Pages: 2743-2750
    |
    Published online on: April 2, 2014
       https://doi.org/10.3892/or.2014.3122
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Abstract

2-(1H-benzimidazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (BMT-1), a bicyclic compound, belongs to the benzimidazole group and consists of the fusion of benzene and imidazole. The objective of the present study was to assess the effect of BMT-1 on the proliferation of multiple myeloma (MM) cells and identify whether BMT-1 induces apoptosis in MM cells. Our results showed a dose- and time-dependent decrease in the proliferation of MM cells treated with BMT-1. Further studies revealed that the antiproliferative effects of BMT-1 were caused by induction of apoptosis with activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in MM cells. In addition, BMT-1 induced the loss of mitochondrial membrane potential resulting in the activation of caspase-8 and -9. Furthermore, the MM cells treated with BMT-1 showed a more acidic intracellular pH (pHi) as indicated by a lower FL1/FL2 ratio caused by inhibition of H+/K+-ATPase. Collectively, these findings demonstrated that a decrease in pHi, caused by H+/K+-ATPase inhibition induced by BMT-1, triggered the dysfunction of the mitochondria resulting in the apoptosis of MM cells. Therefore, BMT-1 may be used as a lead compound for the design and development of new agents with which to treat MM and other forms of cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Yang T, Li M, Liu J, Huang N, Li N, Liu SN, Liu Y, Zhang T, Zou Q, Li H, Li H, et al: Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition. Oncol Rep 31: 2743-2750, 2014.
APA
Yang, T., Li, M., Liu, J., Huang, N., Li, N., Liu, S. ... Li, H. (2014). Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition. Oncology Reports, 31, 2743-2750. https://doi.org/10.3892/or.2014.3122
MLA
Yang, T., Li, M., Liu, J., Huang, N., Li, N., Liu, S., Liu, Y., Zhang, T., Zou, Q., Li, H."Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition". Oncology Reports 31.6 (2014): 2743-2750.
Chicago
Yang, T., Li, M., Liu, J., Huang, N., Li, N., Liu, S., Liu, Y., Zhang, T., Zou, Q., Li, H."Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition". Oncology Reports 31, no. 6 (2014): 2743-2750. https://doi.org/10.3892/or.2014.3122
Copy and paste a formatted citation
x
Spandidos Publications style
Yang T, Li M, Liu J, Huang N, Li N, Liu SN, Liu Y, Zhang T, Zou Q, Li H, Li H, et al: Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition. Oncol Rep 31: 2743-2750, 2014.
APA
Yang, T., Li, M., Liu, J., Huang, N., Li, N., Liu, S. ... Li, H. (2014). Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition. Oncology Reports, 31, 2743-2750. https://doi.org/10.3892/or.2014.3122
MLA
Yang, T., Li, M., Liu, J., Huang, N., Li, N., Liu, S., Liu, Y., Zhang, T., Zou, Q., Li, H."Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition". Oncology Reports 31.6 (2014): 2743-2750.
Chicago
Yang, T., Li, M., Liu, J., Huang, N., Li, N., Liu, S., Liu, Y., Zhang, T., Zou, Q., Li, H."Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition". Oncology Reports 31, no. 6 (2014): 2743-2750. https://doi.org/10.3892/or.2014.3122
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