738 CAPSAICIN, A NOVEL RADIOSENSITIZER, ACTS VIA A TRPV6 MEDIATED MECHANISM
Bibliographic record
Abstract
You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011738 CAPSAICIN, A NOVEL RADIOSENSITIZER, ACTS VIA A TRPV6 MEDIATED MECHANISM Natalie Venier, Alexandra Colquhoun, Hioshi Sasaki, Andrew Loblaw, Neil Fleshner, Laurence Klotz, and Vasundara Venkateswaran Natalie VenierNatalie Venier Toronto, Canada More articles by this author , Alexandra ColquhounAlexandra Colquhoun Toronto, Canada More articles by this author , Hioshi SasakiHioshi Sasaki Toronto, Canada More articles by this author , Andrew LoblawAndrew Loblaw Toronto, Canada More articles by this author , Neil FleshnerNeil Fleshner Toronto, Canada More articles by this author , Laurence KlotzLaurence Klotz Toronto, Canada More articles by this author , and Vasundara VenkateswaranVasundara Venkateswaran Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1707AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radiosensitizing agents sensitize cells to the lethal effects of ionizing radiation (IR). This permits use of lower doses of radiation to achieve equivalent cancer control thereby minimizing adverse effects to normal tissues. Given their lack of toxicity compounds occurring naturally in the diet make ideal potential radiosensitizing agents. Capsaicin, a compound found in the Capsicum sp. of plants, is a widely consumed food additive in areas with low PCa incidence. Traditionally capsaicin is used to treat chronic pain syndromes; however, recently evidence using in vitro PCa models describes its anti-carcinogenic potential. The transient receptor potential vanilloid-receptor (TRPV)-1 and TRPV6 cation selective channels are thought to be partly responsible for mediating these effects. TRPV-1 and TRPV-6 expression is up-regulated in PCa tissue correlating directly with increasing tumor grade. This suggests TRPV1 and/or TRPV6 may be potential therapeutic targets for capsaicin mediated interventions in PCa patients. As IR and capsaicin both promote apoptosis and inhibit cell cycle progression in vitro we hypothesize an at least additive effect of combining these two therapies. METHODS Using clonogenic assays we assessed the effect of ionizing radiation (1–8 Gy) and/or capsaicin (1–10ìM) on colony formation rates in 4 human PCa cell lines (LNCaP, PC3, PC3AR2, DU145). Proliferative, apoptotic, TRPV-6 protein markers were assessed using Western blot analyses. RESULTS Exposure of cells to capsaicin (1–10ìM) or IR (1–8 Gy) caused significant dose-dependent inhibition of colony formation (p<0.001). Combining capsaicin with IR resulted in further significant inhibition of colony formation rates (P<0.001). Western blot analyses showed LNCaP cells treated with capsaicin and/or IR to have increased expression of pro-apoptotic proteins BAX and Bad, tumor-suppressor proteins p21 and p27 and reduced androgen-receptor. Additionally, capsaicin monotherapy caused a dramatic alteration in TRPV1 and TRPV6 expression. CONCLUSIONS These studies confirm the radiosensitizing capacity of capsaicin in PCa cells in vitro. Ongoing studies using are further delineating the mechanism of interaction of these treatment modalities. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e296-e297 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Natalie Venier Toronto, Canada More articles by this author Alexandra Colquhoun Toronto, Canada More articles by this author Hioshi Sasaki Toronto, Canada More articles by this author Andrew Loblaw Toronto, Canada More articles by this author Neil Fleshner Toronto, Canada More articles by this author Laurence Klotz Toronto, Canada More articles by this author Vasundara Venkateswaran Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.086 | 0.019 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".