Chemopreventive Effect of Bitter Melon (Momordica charantia) Juice on Pancreatic Carcinogenesis in LSL-KrasG12D /+; p48Cre/+ Mice.

Herein, using the LSL-KrasG12D/+; p48Cre/+ 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-KrasG12D/+; p48Cre/+ 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.