ArticleCell death & disease2016
Flavonol and imidazole derivatives block HPV16 E6 activities and reactivate apoptotic pathways in HPV⁺ cells.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- 30-hydroxygambogic acid activates overlapping and independent apoptotic pathways in HPV positive and HPV negative oral cancer cells.Tumour virus research · 2026Article
- Topical administration of in situ gelling formulation containing myricetin-polycarboxylate nanoparticles inhibits murine genital herpes infection.International journal of pharmaceutics · 2026Article
- The Exploration of Therapeutic Antivirals for Human Papillomavirus in the Last 40 Years: Bibliometric Research.Pathogens (Basel, Switzerland) · 2026Article
- Targeting HPV for the prevention, diagnosis, and treatment of cervical cancer.Journal of molecular cell biology · 2025Review
- Human papilloma virus (HPV) mediated cancers: an insightful update.Journal of translational medicine · 2025Review
- A Combination of Flavonoids Suppresses Cell Proliferation and the E6 Oncogenic Pathway in Human Papillomavirus-Transformed Cells.Pathogens (Basel, Switzerland) · 2025Article
- Small Molecule Inhibitors of Human Papillomavirus: A Review of Research from 1997 to 2021.Current medicinal chemistry · 2024Review
- Discovery of reactive peptide inhibitors of human papillomavirus oncoprotein E6.Chemical science · 2023Article
- GA-OH enhances the cytotoxicity of photon and proton radiation in HPVFrontiers in oncology · 2023Article
- NF-Y Subunits Overexpression in HNSCC.Cancers · 2021Article
- PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6.Molecules (Basel, Switzerland) · 2021Review
- A high-content AlphaScreen™ identifies E6-specific small molecule inhibitors as potential therapeutics for HPVOncotarget · 2021Article
- ACE2 : S1 RBD Interaction-Targeted Peptides and Small Molecules as Potential COVID-19 Therapeutics.Advances in pharmacological and pharmaceutical sciences · 2021Article
- Targeted Therapy as a Potential De-Escalation Strategy in Locally Advanced HPV-Associated Oropharyngeal Cancer: A Literature Review.Frontiers in oncology · 2021Review
- Effects of HPV16 E6 protein on Daxx-induced apoptosis in C33A cells.Cellular & molecular biology letters · 2020Article
- Nb-induced stabilisation of p53 in HPV-infected cells.Scientific reports · 2019Article
- Identification of potential binding pocket on viral oncoprotein HPV16 E6: a promising anti-cancer target for small molecule drug discovery.BMC molecular and cell biology · 2019Article
- Molecular modeling simulation studies reveal new potential inhibitors against HPV E6 protein.PloS one · 2019Article
- A quantitative LumiFluo assay to test inhibitory compounds blocking p53 degradation induced by human papillomavirus oncoprotein E6 in living cells.Scientific reports · 2018Article
- RBBP6 expressional effects on cell proliferation and apoptosis in breast cancer cell lines with distinct p53 statuses.Cancer management and research · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-risk human papillomaviruses (HR-HPVs) cause nearly all cases of cervical cancer, as well as approximately 30% of head and neck cancers. HPV 16 E6, one of two major viral oncogenes, protects cells from apoptosis by binding to and accelerating the degradation of several proteins important in apoptotic signaling, including caspase 8 and p53. We proposed that blocking the interactions between HPV E6 and its partners using small molecules had the potential to re-sensitize HPV(+) cells to apoptosis. To test this idea, we screened libraries of small molecules for candidates that could block E6/caspase 8 binding and identified several candidates from different chemical classes. We tested hits for dose-dependency and specificity in vitro and for toxicity in a cell-based assay and then used this information to select the two best candidates for further testing: myricetin, a flavonol, and spinacine, an imidazole amino-acid derivative of histidine. Both compounds clearly inhibited the ability of E6 to bind in vitro to both caspase 8 and E6AP, the protein that mediates p53 degradation. In addition, both compounds were able to increase the level of caspase 8 and p53 in SiHa cervical cancer cells, resulting in an increase of caspase 3/7 activity. Finally, both myricetin and spinacine sensitized HPV(+) cervical and oral cancer cells, but not HPV(-) cervical and oral cancer cells, to apoptosis induced by the cancer-specific ligand TRAIL, as well as the chemotherapeutic agents doxorubicin and cisplatin. New therapies based on this work may improve treatment for HPV(+) cancer patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.