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B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB

  • Authors:
    • Meng-Hsuan Cheng
    • Yun-Hong Wong
    • Chia-Ming Chang
    • Chun-Chien Yang
    • Shih-Hua Chen
    • Chun-Lung Yuan
    • Hsiao-Mei Kuo
    • Chun-Yuh Yang
    • Hui-Fen Chiu
  • View Affiliations / Copyright

    Affiliations: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan, R.O.C., Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C., Department of Chemistry, Republic of China Military Academy, Fengshan, Kaohsiung 83059, Taiwan, R.O.C., Department of Neuroscience, Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan, R.O.C., Faculty of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C.
    Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1137-1148
    |
    Published online on: April 7, 2017
       https://doi.org/10.3892/ijmm.2017.2946
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Abstract

We previously demonstrated that B1 induced significant cytotoxic effects, cell cycle G1 arrest and apoptosis in human lung cancer A549 cells through the inhibition of DNA topoisomerase II activity. In the present study, we focused on the histone deacetylase (HDAC) modulation of B1 in A549 cells. HDACs, important enzymes affecting epigenetic regulation, play a crucial role in human carcinogenesis. Our findings showed that B1 could suppress the growth of A549 cells in vitro through the inhibition of HDAC activity. Additionally, B1 caused disruption of the mitochondrial membrane potential and induced DNA double-strand breaks (DSBs) in a dose- and time-dependent manner, which consequently led to cell apoptosis. We also observed that B1 inhibited cancer cell migration and angiogenesis-related signal expression, including vascular endothelial growth factor (VEGF) and pro-matrix metalloproteinases-2 and -9 (pro-MMP-2/9). Gelatin zymography suggested that B1 decreased pro-MMP-2 and pro-MMP-9 activity. Transcription factors, signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB), are vital players in the many steps of carcinogenesis. B1 showed significant dose-response inhibitory effects on cytoplasmic expression and nuclear translocation of both phosphorylated STAT3 (pSTAT3) and NF-κB. It has been well documented that reactivated telomerase confers cancer cells the ability to repair DNA. Real-time PCR results indicated that B1 inhibited STAT3 and NF-κB mRNA expression and telomerase activity. Taken together, our results demonstrated that B1 exerted significant inhibitory effects on HDAC, telomerase activities, oncogenic STAT3 and NF-κB expression. The inhibition of the intricate crosstalk between STAT3 and NF-κB may be a major factor in the molecular action mechanism of B1. The multiple targeting effects of B1 render it a potential new drug for lung cancer therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Cheng M, Wong Y, Chang C, Yang C, Chen S, Yuan C, Kuo H, Yang C and Chiu H: B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB. Int J Mol Med 39: 1137-1148, 2017.
APA
Cheng, M., Wong, Y., Chang, C., Yang, C., Chen, S., Yuan, C. ... Chiu, H. (2017). B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB. International Journal of Molecular Medicine, 39, 1137-1148. https://doi.org/10.3892/ijmm.2017.2946
MLA
Cheng, M., Wong, Y., Chang, C., Yang, C., Chen, S., Yuan, C., Kuo, H., Yang, C., Chiu, H."B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB". International Journal of Molecular Medicine 39.5 (2017): 1137-1148.
Chicago
Cheng, M., Wong, Y., Chang, C., Yang, C., Chen, S., Yuan, C., Kuo, H., Yang, C., Chiu, H."B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB". International Journal of Molecular Medicine 39, no. 5 (2017): 1137-1148. https://doi.org/10.3892/ijmm.2017.2946
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng M, Wong Y, Chang C, Yang C, Chen S, Yuan C, Kuo H, Yang C and Chiu H: B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB. Int J Mol Med 39: 1137-1148, 2017.
APA
Cheng, M., Wong, Y., Chang, C., Yang, C., Chen, S., Yuan, C. ... Chiu, H. (2017). B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB. International Journal of Molecular Medicine, 39, 1137-1148. https://doi.org/10.3892/ijmm.2017.2946
MLA
Cheng, M., Wong, Y., Chang, C., Yang, C., Chen, S., Yuan, C., Kuo, H., Yang, C., Chiu, H."B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB". International Journal of Molecular Medicine 39.5 (2017): 1137-1148.
Chicago
Cheng, M., Wong, Y., Chang, C., Yang, C., Chen, S., Yuan, C., Kuo, H., Yang, C., Chiu, H."B1, a novel HDAC inhibitor, induces apoptosis through the regulation of STAT3 and NF-κB". International Journal of Molecular Medicine 39, no. 5 (2017): 1137-1148. https://doi.org/10.3892/ijmm.2017.2946
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