Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes

Int J Mol Med. 2021 Jan;47(1):335-345. doi: 10.3892/ijmm.2020.4789. Epub 2020 Nov 17.

Abstract

Resveratrol is a representative polyphenol of diet‑derived putative cancer chemopreventive agents, which have attracted increasing interest in the cancer chemoprevention community. The inhibition of the action of human papillomavirus (HPV) E6 and E7 has been considered a key approach for cervical cancer therapy. Resveratrol has been shown to induce the apoptosis, and reduce both the viability and mitotic index of a number of cancer cell lines, including human cervical cancer cells. In the present study, it was confirmed that resveratrol inhibited the HPV E6 mRNA, HPV E6 protein and phosphorylated retinoblastoma protein (p‑pRb1) levels, and increased the p53 protein levels in HeLa and Ca Ski cells, as well as in subcutaneous tumor tissue grown from HeLa cells. High‑risk HPV uses a bicistronic RNA to control E6 and E7 genes simultaneously. On the whole, the present study demonstrates that resveratrol inhibits cervical cancer development by suppressing the transcription and translation of E6 and E7, and also by promoting the apoptosis and G1/S phase transition arrest. These findings may provide the basis for the development of resveratrol as a candidate for cervical cancer therapy.

Keywords: resveratrol; cervical cancer; human papillomavirus E6 and E7; cell apoptosis; cell cycle arrest.

MeSH terms

  • DNA-Binding Proteins / biosynthesis*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Viral / drug effects*
  • HeLa Cells
  • Human papillomavirus 18 / metabolism*
  • Humans
  • Oncogene Proteins, Viral / biosynthesis*
  • Resveratrol / pharmacology*
  • Transcription, Genetic / drug effects*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 18
  • E7 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Resveratrol