Rice bran, removed from whole grain rice for white rice milling, has demonstrated efficacy for the control and suppression of colitis and colon cancer in multiple animal models. Dietary rice bran intake was shown to modify human stool metabolites as a result of modifications to metabolism by gut microbiota. In this study, human stool microbiota from colorectal cancer (CRC) survivors that consumed rice bran daily was examined by fecal microbiota transplantation (FMT) for protection from azoxymethane and dextran sodium sulfate (AOM/DSS) induced colon carcinogenesis in germ-free mice. Mice transfaunated with rice bran-modified microbiota communities (RMC) harbored fewer neoplastic lesions in the colon and displayed distinct enrichment of Flavonifractor and Oscillibacter associated with colon health, and the depletion of Parabacteroides distasonis correlated with increased tumor burden. Two anti-cancer metabolites, myristoylcarnitine and palmitoylcarnitine were increased in the colon of RMC transplanted mice. Trimethylamine-N-oxide (TMAO) and tartarate that are implicated in CRC development were reduced in murine colon tissue after FMT with rice bran-modified human microbiota. Findings from this study show that rice bran modified gut microbiota from humans confers protection from colon carcinogenesis in mice and suggests integrated dietary-FMT intervention strategies should be tested for colorectal cancer control, treatment, and prevention.

Kushal Kandhari, Sandeep Paudel, Komal Raina, Chapla Agarwal, Rama Kant, Michael F. Wempe, Cindy O’Bryant, Rajesh Agarwal. J Cancer Prev 2021;26:266-76. https://doi.org/10.15430/JCP.2021.26.4.266

The consumption of the non-steroidal anti-inflammatory drug (NSAID) aspirin is associated with a significant reduction in the risk of developing TMPRSS2-ERG (fusion)-positive prostate cancer (PCa) compared to fusion-negative PCa in population-based case–control studies; however, no extensive preclinical studies have been conducted to investigate and confirm these protective benefits. Thus, the focus of this study was to determine the potential usefulness of aspirin and another NSAID, naproxen, in PCa prevention, employing preclinical models of both TMPRSS2-ERG (fusion)-driven (with conditional deletion of Pten) and non-TMPRSS2-ERG-driven (Hi-Myc^+/− mice) PCa. Male mice (n = 25 mice/group) were fed aspirin- (700 and 1400 ppm) and naproxen- (200 and 400 ppm) supplemented diets from (a) 6 weeks until 32 weeks of Hi-Myc^+/− mice age; and (b) 1 week until 20 weeks post-Cre induction in the fusion model. In all NSAID-fed groups, compared to no-drug controls, there was a significant decrease in higher-grade adenocarcinoma incidence in the TMPRSS2-ERG (fusion)-driven PCa model. Notably, there were no moderately differentiated (MD) adenocarcinomas in the dorsolateral prostate of naproxen groups, and its incidence also decreased by ~79–91% in the aspirin cohorts. In contrast, NSAIDs showed little protective effect against prostate tumorigenesis in Hi-Myc^+/− mice, suggesting that NSAIDs exert a specific protective effect against TMPRSS2-ERG (fusion)-driven PCa.

Herein, using the LSL‐Kras ^G12D/+ ; p48 ^Cre/+ transgenic mouse model [that recapitulates the full spectrum of human disease, progressing from early pancreatic intraepithelial neoplasia lesions to invasive pancreatic ductal adenocarcinoma (PDAC)], we determined the chemopreventive effect of long‐term (chronic) administration of Bitter Melon Juice (BMJ‐standardized lyophilized juice processed from the fruits of Momordica charantia ) against pancreatic cancer. Starting at 6 weeks of age, female LSL‐Kras ^G12D/+ ; p48 ^Cre/+ mice were subjected to BMJ intervention (oral gavage, dose: 200 mg/kg body wt., 5 days/week) for 35 weeks (study end: 41 weeks of age), and pathological and molecular changes in the pancreas were assessed. Results indicated that BMJ shifted the pancreatic tumor profile from moderately differentiated adenocarcinoma in controls towards a more heterogeneous profile enriched for well‐differentiated lesions indicating that prolonged exposure to BMJ bioactives results in a less aggressive phenotype. BMJ significantly reduced proliferative index (~24%) and induced a ~ 4‐fold increase in apoptosis in the pancreas. The effects on AMPK activation (~2‐fold increase) and decrease in the expression of [glucose (GLUT‐1) and lactate (MCT‐4) transporter levels (∼49%–69%,), NF‐κB/p65 (~40%), EMT marker‐Vimentin (~46%), fibrotic microenvironment marker (α‐SMA, ~29%) and Mucin‐1 (MUC‐1, ~45%)] indicate that BMJ modulates several interconnected pathways essential for PDAC growth and progression. Plasma proteomic profiling indicated that Fractalkine (CX3CL1), MIP‐3β (CCL19), MIP‐3α (CCL20), and SCF were decreased by BMJ, while Axl and TNF‐alpha were overexpressed in BMJ‐treated animals compared to positive controls. These results encourage further research into bitter melon compounds as a potential chemopreventive option for pancreatic cancer, especially for high‐risk groups.