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

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&NA; 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… Click to show full abstract

&NA; 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: c646 inhibited; cervical cancer; hpv genes; p300; cancer

Journal Title: European Journal of Pharmacology
Year Published: 2017

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