Evidence map›Paper›PMID 24434067›Full record

ArticleOral oncology2014

Vanilloids induce oral cancer apoptosis independent of TRPV1.

Cara B Gonzales, Nameer B Kirma, Jorge J De La Chapa, Richard Chen, Michael A Henry, Songjiang Luo, Kenneth M Hargreaves

Abstract read
In one paragraph

Article in Oral oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Capsaicin intake and oral carcinogenesis: A systematic review.Medicina oral, patologia oral y cirugia bucal · 2021
    Pooled it
  2. The Impact of TRPV1 on Cancer Pathogenesis and Therapy: A Systematic Review.International journal of biological sciences · 2021
    Pooled it
  3. Review
  4. Article
  5. Article
  6. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Anticancer Activity of Region B Capsaicin Analogs.Journal of medicinal chemistry · 2023
    Review
  16. Review
  17. Inhibition of CaFrontiers in physiology · 2022
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Cara B GonzalesCancer Therapy and Research Center, UTHSCSA, San Antonio, TX 78229, USA; Comprehensive Dentistry, UTHSCSA Dental School, San Antonio, TX 78229, USA. Electronic address: gonzalesc5@uthscsa.edu.
Nameer B KirmaCancer Therapy and Research Center, UTHSCSA, San Antonio, TX 78229, USA; Molecular Medicine, UTHSCSA, San Antonio, TX 78229, USA.
Jorge J De La ChapaComprehensive Dentistry, UTHSCSA Dental School, San Antonio, TX 78229, USA.
Richard ChenComprehensive Dentistry, UTHSCSA Dental School, San Antonio, TX 78229, USA.
Michael A HenryEndodontics, UTHSCSA Dental School, San Antonio, TX 78229, USA.
Songjiang LuoComprehensive Dentistry, UTHSCSA Dental School, San Antonio, TX 78229, USA.
Kenneth M HargreavesEndodontics, UTHSCSA Dental School, San Antonio, TX 78229, USA; Pharmacology, UTHSCSA Dental School, San Antonio, TX 78229, USA.
The University of Texas Health Science Center at San Antonio · US

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Robin Jean Leach · 1991 to 2026
$59.1M
Institute for Integration of Medicine & Science: A Partnership to Improve HealthUL1TR001120 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CLARK, ROBERT A, HARGREAVES, KENNETH M · 2013 to 2017
$16.5M
Institute for Integration of Medicine & Science: A Partnership to Improve HealthUL1TR000149 · NCATS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CLARK, ROBERT A · 2012 to 2013
$6.8M
NCATS NIH HHS UL1 TR000149NCATS NIH HHS UL1TR000149NCATS NIH HHS UL1 TR001120NCI NIH HHS CA054174NCI NIH HHS P30 CA054174
6 · The paper itself

Abstract

objectiveTo investigate the mechanisms of vanilloid cytotoxicity and anti-tumor effects in oral squamous cell carcinoma (OSCC). MATERIALS AND

methodsImmunohistochemistry and qPCR analyses demonstrated expression of the TRP vanilloid type 1 (TRPV1) receptor in OSCC. Using cell proliferation assays, calcium imaging, and three mouse xenograft models, prototypical vanilloid agonist (capsaicin) and antagonist (capsazepine) were evaluated for cytotoxic and anti-tumor effects in OSCC.

resultsOSCC cell lines treated with capsaicin displayed significantly reduced cell viability. Pre-treatment with capsazepine failed to reverse these effects. Moreover, capsazepine alone was significantly cytotoxic to tumor cells, suggesting the mechanism-of-action is independent of TRPV1 activation. This was further confirmed by calcium imaging indicating that TRPV1 channels are not functional in the cell lines tested. We then examined whether the observed vanilloid cytotoxicity was due to the generation of reactive oxygen species (ROS) and subsequent apoptosis. Induction of ROS was confirmed by flow cytometry and reversed by co-treatment with the antioxidant N-acetyl-cysteine (NAC). NAC also significantly reversed vanilloid cytotoxicity in cell proliferation assays. Dose-dependent induction of apoptosis with capsazepine treatment was demonstrated by FACS analyses and c-PARP expression in treated cells. Our in vivo xenograft studies showed that intra-tumoral injections of capsazepine exhibited high effectiveness in suppressing tumor growth with no identifiable toxicities.

conclusionsThese findings confirm TRPV1 channel expression in OSCC. However anti-tumor effects of vanilloids are independent of TRPV1 activation and are most likely due to ROS induction and subsequent apoptosis. Importantly, these studies demonstrate capsazepine is a potential therapeutic candidate for OSCC.

Indexed as

AnimalsApoptosisCapsaicinCarcinoma, Squamous CellDiterpenesHumansMiceMouth NeoplasmsPolymerase Chain ReactionTRPV Cation ChannelsXenograft Model Antitumor AssaysCapsaicinDiterpenesTRPV1 protein, humanTRPV Cation ChannelsApoptosisCapsaicinCapsazepineOral cancerTRPV1

Identifiers

PMID24434067
PMCPMC4418484
OpenAlexW2015128691

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.