{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T10:49:27Z","timestamp":1791802167999,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA195708"],"award-info":[{"award-number":["R01CA195708"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Herein, using the LSL\u2010Kras\n                    <jats:sup>G12D\/+<\/jats:sup>\n                    ; p48\n                    <jats:sup>Cre\/+<\/jats:sup>\n                    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\u2010term (chronic) administration of Bitter Melon Juice (BMJ\u2010standardized lyophilized juice processed from the fruits of\n                    <jats:italic>Momordica charantia<\/jats:italic>\n                    ) against pancreatic cancer. Starting at 6 weeks of age, female LSL\u2010Kras\n                    <jats:sup>G12D\/+<\/jats:sup>\n                    ; p48\n                    <jats:sup>Cre\/+<\/jats:sup>\n                    mice were subjected to BMJ intervention (oral gavage, dose: 200\u2009mg\/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\u2010differentiated lesions indicating that prolonged exposure to BMJ bioactives results in a less aggressive phenotype. BMJ significantly reduced proliferative index (~24%) and induced a\u2009~\u20094\u2010fold increase in apoptosis in the pancreas. The effects on AMPK activation (~2\u2010fold increase) and decrease in the expression of [glucose (GLUT\u20101) and lactate (MCT\u20104) transporter levels (\u223c49%\u201369%,), NF\u2010\u03baB\/p65 (~40%), EMT marker\u2010Vimentin (~46%), fibrotic microenvironment marker (\u03b1\u2010SMA, ~29%) and Mucin\u20101 (MUC\u20101, ~45%)] indicate that BMJ modulates several interconnected pathways essential for PDAC growth and progression. Plasma proteomic profiling indicated that Fractalkine (CX3CL1), MIP\u20103\u03b2 (CCL19), MIP\u20103\u03b1 (CCL20), and SCF were decreased by BMJ, while Axl and TNF\u2010alpha were overexpressed in BMJ\u2010treated 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\u2010risk groups.\n                  <\/jats:p>","DOI":"10.1002\/mc.70164","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T19:05:06Z","timestamp":1786388706000},"page":"1383-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemopreventive Effect of Bitter Melon (Momordica charantia) Juice on Pancreatic Carcinogenesis in LSL\u2010Kras\n                    <sup>G12D<\/sup>\n                    <sup>\/+<\/sup>\n                    ; p48\n                    <sup>Cre\/+<\/sup>\n                    Mice"],"prefix":"10.1002","volume":"65","author":[{"given":"Lakshmi Sai Pratyusha","family":"Bugata","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences South Dakota State University Brookings South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepanshi","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0550-1467","authenticated-orcid":false,"given":"Rama","family":"Kant","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences South Dakota State University Brookings South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Imtiazul","family":"Kabir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences South Dakota State University Brookings South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1146-4890","authenticated-orcid":false,"given":"Chapla","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9455-0235","authenticated-orcid":false,"given":"Rajesh","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Anschutz Medical Campus Aurora Colorado USA"},{"name":"University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0371-1070","authenticated-orcid":false,"given":"Komal","family":"Raina","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences South Dakota State University Brookings South Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70043"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v12.i2.173"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2018.1428093"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00516-8"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.22"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136760"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.014"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2011.645806"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2020.03.025"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-015-0388-3"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2016.07.002"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23251"},{"issue":"9","key":"e_1_2_13_14_1","first-page":"1164","article-title":"Bitter Melon Juice\u2010Intake Modulates Glucose Metabolism and Lactate Efflux in Tumors in Its Efficacy Against Pancreatic Cancer","volume":"40","author":"Dhar D.","year":"2019","journal-title":"Carcinogenesis"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22833"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgt081"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2015.2885"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.15430\/JCP.2021.26.4.266"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.121026"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-10-0038"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000533"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00309-X"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.04.023"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.12"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0370605"},{"key":"e_1_2_13_26_1","article-title":"PCNA Inhibition Enhances the Antitumor Activity of KRAS\u2010Targeted Therapies in Pancreatic Cancer","volume":"1","author":"Bannoura S. 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