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

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.

SUBMITTER: Sun X

PROVIDER: S-EPMC7723400 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Sun Xiaodong X Fu Pan P Xie Lixia L Chai Senmao S Xu Qianqian Q Zeng Lian L Wang Xuanbin X Jiang Nan N Sang Ming M

International journal of molecular medicine 20201117 1

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 presen ...[more]

PMID: 33236130

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Project description:Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001). These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay's high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among young women) or when 'LSIL vs. HSIL' assignment is equivocal.

Project description:BackgroundGenital infection with certain types of Human papillomavirus (HPV) is a major cause of cervical cancer globally. For early detection of premalignant dysplasia, evidences are coming out on the usefulness of HPV E6/E7 mRNA test as a potential tool compared with cytology and HPV DNA testing. Taking into account shortage of compiled data on this field, the aim of this systematic review was to describe the latest diagnostic performance of HPV E6/E7 mRNA testing to detect high grade cervical lesions (CIN2+) where by histology was taken as a gold standard.MethodsArticles published in English were systematically searched using key words from PubMed/Medline and SCOPUS. In addition, Google Scholar and the Google database were searched manually for grey literature. Two reviewers independently assessed study eligibility, risk of bias and extracted the data. We performed a descriptive presentation of the performance of E6/E7 mRNA test (in terms of sensitivity, specificity, negative and positive predictive values) for the detection of CIN2 + .ResultsOut of 231 applicable citations, we have included 29 articles that included a total of 23,576 study participants (age range, 15-84 years) who had different cervical pathologies. Among the participants who had cervical histology, the proportion of CIN2+ was between 10.6 and 90.6%. Using histology as a gold standard, 11 studies evaluated the PreTect HPV Proofer, 7 studies evaluated the APTIMA HPV assay (Gen-Probe) and 6 studies evaluated the Quantivirus® HPV assay. The diagnostic performance of these three most common mRNA testing tools to detect CIN2+ was; 1) PreTect Proofer; median sensitivity 83%, specificity 73%, PPV 70 and NPV 88.9%. 2) APTIMA assay; median sensitivity 91.4%, specificity 46.2%, PPV 34.3% and NPV 96.3%. 3) Quantivirus®: median sensitivity 86.1%, specificity 54.6%, PPV 54.3% and NPV was at 89.3%. Further, the area under the receiver operating characteristics (AU-ROC) curve varied between 63.8 and 90.9%.ConclusionsThe reported diagnostic accuracy implies that HPV mRNA based tests possess diagnostic relevance to detect CIN2+ and could potentially be considered in areas where there is no histology facility. Further studies including its cost should be considered.

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

Publications

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

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