Selective p300 inhibitor C646 inhibited HPV E6-E7 genes, altered glucose metabolism and induced apoptosis in cervical cancer cells

  • Eur J Pharmacol. 2017 Oct 5;812:206-215. doi: 10.1016/j.ejphar.2017.06.005.
Hongpeng He  1 Yongwei Lai  1 Yunpeng Hao  1 Yupeng Liu  1 Zijiang Zhang  1 Xiang Liu  1 Chenhong Guo  1 Mengmeng Zhang  1 Hao Zhou  1 Nan Wang  1 Xue-Gang Luo  1 Lihong Huo  1 Wenjian Ma  1 Tong-Cun Zhang  2
Affiliations
  • 1. Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China.
  • 2. Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China; College of Life Sciences, Wuhan University of Science and Technology, Wuhan 430081, PR China. Electronic address: [email protected].
Abstract

High risk HPV Infection is a causative factor of cervical Cancer. The constitutive expression of HPV E6-E7 genes is important for the maintenance of Cancer phenotypes. The cellular transcription co-activator p300 plays a crucial role in the regulation of HPV genes thus it was targeted for the inhibition of HPV-associated cervical Cancer. In the present study, HPV positive cervical cells were treated with C646, a selective inhibitor of p300, to investigate its influence on HPV E6-E7 expression and Cancer cell growth. Results of RT-qPCR, Western-blot and promoter activity assays showed that C646 inhibited the transcription of HPV E6-E7, which was accompanied with the accumulation of p53 protein. Meanwhile, cell proliferation was suppressed, glucose metabolism was disrupted and Apoptosis was induced via the intrinsic pathway. Generally, the anti-cervical Cancer potential of C646 was demonstrated and a novel mechanism was proposed in this study.

Keywords
Cervical cancer; Glycolysis; HPV E6-E7; P300 inhibitor; P53 accumulation.
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