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Published on: July 5, 2017
Suppression of Proinflammatory and Prosurvival Biomarkers in Oral Cancer Patients Consuming a Black Raspberry
Thomas J Knobloch1, Lana K Uhrig2, Dennis K Pearl3
1The Ohio State University, Columbus, Ohio. Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio. knobloch.1@osu.edu.
Abstract:
Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food-based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder from the time of enrollment to the date of curative intent surgery (13.9 ± 1.27 days). Transcriptional biomarkers were evaluated in patient-matched OSCCs and noninvolved high at-risk mucosa (HARM) for BRB-associated changes. Significant expression differences between baseline OSCC and HARM tissues were confirmed using a panel of genes commonly deregulated during oral carcinogenesis. Following BRB troche administration, the expression of prosurvival genes (AURKA, BIRC5, EGFR) and proinflammatory genes (NFKB1, PTGS2) were significantly reduced. There were no BRB-associated grade 3-4 toxicities or adverse events, and 79.2% (N = 30) of patients successfully completed the study with high levels of compliance (97.2%). The BRB phytochemicals cyanidin-3-rutinoside and cyanidin-3-xylosylrutinoside were detected in all OSCC tissues analyzed, demonstrating that bioactive components were successfully reaching targeted OSCC tissues. We confirmed that hallmark antiapoptotic and proinflammatory molecular biomarkers were overexpressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. As these molecular biomarkers are fundamental to oral carcinogenesis and are modifiable, they may represent emerging biomarkers of molecular efficacy for BRB-mediated oral cancer chemoprevention.
Insights
Black raspberries (BRB) deliver cancer-fighting compounds to oral tissues, reducing key gene markers linked to oral cancer development. This study confirms BRB
Area of Science:
- Oncology
- Nutritional Science
- Molecular Biology
Background:
- Black raspberries (BRB) show promise in preventing aerodigestive tract cancers in animal models.
- Translational research on BRB phytochemicals in oral mucosa is limited.
- Oral cancer prevention strategies require understanding phytochemical delivery and molecular impact.
Purpose of the Study:
- To determine if BRB phytochemicals reach oral tissues.
- To assess the effect of BRB on proinflammatory and antiapoptotic gene expression in oral cancer.
- To identify potential molecular biomarkers for BRB-mediated chemoprevention.
Main Methods:
- Phase 0 clinical trial involving patients with oral squamous cell carcinoma (OSCC).
- Administration of oral troches containing freeze-dried BRB powder before surgery.
- Evaluation of gene expression in matched OSCC and high at-risk mucosa (HARM) tissues.
- Detection of specific BRB phytochemicals in tumor tissues.
Main Results:
- BRB phytochemicals (cyanidin-3-rutinoside, cyanidin-3-xylosylrutinoside) were detected in all analyzed OSCC tissues.
- Significant reduction in prosurvival (AURKA, BIRC5, EGFR) and proinflammatory (NFKB1, PTGS2) gene expression post-BRB administration.
- No significant toxicities or adverse events reported; high patient compliance.
- Confirmed overexpression of antiapoptotic and proinflammatory biomarkers in OSCC, reduced by BRB.
Conclusions:
- BRB phytochemicals successfully reach targeted oral cancer tissues.
- BRB administration modulates key molecular pathways involved in oral carcinogenesis.
- Modifiable molecular biomarkers show potential for assessing BRB efficacy in oral cancer chemoprevention.
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