Suppression of Proinflammatory and Prosurvival Biomarkers in Oral Cancer Patients Consuming a Black Raspberry Phytochemical-Rich Troche

Abstract

Black raspberries (BRBs) 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 pro-inflammatory and anti-apoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCCs) 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 non-involved 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 pro-survival genes (AURKA, BIRC5, EGFR) and pro-inflammatory 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 anti-apoptotic and pro-inflammatory molecular biomarkers were over-expressed in OSCCs and that their gene expression was significantly reduced following BRB troche administration. Since 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.

Chemopreventive Effect of Green Tea and Curcumin in Induced Oral Squamous Cell Carcinoma: An Experimental Study

“…Several natural compounds and micronutrients (green tea extract, curcumin, resveratrol, broccoli sprout extract, soybean extracts, vitamin E, vitamin C, lyophilized black raspberries and pomegranate juice) have been under investigation for their adequacy in oral cancer chemoprevention (6,7). These compounds contain high levels of polyphenols with anti-oxidant, anti-migratory, antiproliferative and anti-invasive effects on cancer cell properties and are proposed to restrain carcinogenesis through their action on downstream signaling pathways (8).…”

Phytotherapeutics in cancer invasion and metastasis

“…A black raspberry ( Rubus occidentalis L.) formulation (rich in cyanidin‐3‐rutinoside and cyanidin‐3‐xylosylrutinoside) was administered to oral squamous cell carcinoma patients. Modulation of antiapoptotic and proinflammatory genes AURKA, BIRC5, EGFR, NFKB1, and PTGS2 was reported, and no adverse effect was observed (Gu et al, ; Knobloch et al, ).…”

Protective Role of Dietary Berries in Cancer

“…Knobloch and co-workers in a phase 0 human study showed that black raspberries, when administered as freeze-dried powder supplement in oral torches to oral cancer biopsy-confirmed patients, improve gene expression profile associated with oral cancer [86]. Transcriptional biomarkers assessed showed significant improvement for the berry supplemented diet demonstrating marked reduction for the pro-inflammatory genes NFKB1, PTGS2 as well as pro-survival genes AURKA, BIRC5, EGFR all strongly associated with oral cancer risk and progression [86].…”

“…Transcriptional biomarkers assessed showed significant improvement for the berry supplemented diet demonstrating marked reduction for the pro-inflammatory genes NFKB1, PTGS2 as well as pro-survival genes AURKA, BIRC5, EGFR all strongly associated with oral cancer risk and progression [86]. …”