Addressed. Division of Pharmaceutical Sciences, Skaggs College of Pharmacy and Pharmaceutical Sciences, University of Colorado, 12850 E. Montview Blvd, Area V202118, Box C238, Aurora, CO 80045, USA. Tel: 3037244057; Fax: 3037247266; E-mail: [email protected] of pancreatic cancer is extremely poor, suggesting critical needs for additional drugs to improve disease outcome. In this study, we examined efficacy and linked mechanism of a novel agent bitter melon juice (BMJ) against pancreatic carcinoma cells each in culture and nude mice. BMJ anticancer efficacy was analyzed in human pancreatic carcinoma BxPC3, MiaPaCa2, AsPC1 and Capan2 cells by 3(four,5dimethylthiazole2yl)two,5diphenyl tetrazolium bromide, cell death enzymelinked immunosorbent assay and annexin/propidium iodide assays. BMJ impact on apoptosis regulators was assessed by immunoblotting. In vivo BMJ efficacy was evaluated against MiaPaCa2 tumors in nude mice, and xenograft was analyzed for biomarkers by immunohistochemistry (IHC). Benefits showed that BMJ (2 v/v) decreases cell viability in all 4 pancreatic carcinoma cell lines by inducing sturdy apoptotic death. At molecular level, BMJ caused caspases activation, altered expression of Bcl2 family members and cytochromec release in to the cytosol. On top of that, BMJ decreased survivin and Xlinked inhibitor of apoptosis protein but increased p21, CHOP and phosphorylated mitogenactivated protein kinases (extracellular signalregulated kinase 1/2 and p38) levels. Importantly, BMJ activated adenosine monophosphateactivated protein kinase (AMPK), a biomarker for cellular energy status, and an AMPK inhibitor (Compound C) reversed BMJinduced caspase3 activation suggesting activated AMPK involvement in BMJinduced apoptosis. In vivo, oral administration of lyophilized BMJ (5 mg in 100 water/day/ mouse) for 6 weeks inhibited MiaPaCa2 tumor xenograft growth by 60 (P 0.01) without noticeable toxicity in nude mice. IHC analyses of MiaPaCa2 xenografts showed that BMJ also inhibits proliferation, induces apoptosis and activates AMPK in vivo. General, BMJ exerts strong anticancer efficacy against human pancreatic carcinoma cells, each in vitro and in vivo, suggesting its clinical usefulness.Introduction Pancreatic cancer is an aggressive malignancy that develops within a relatively symptomfree manner and is normally at advanced stage at the time of diagnosis.(3-Chloronaphthalen-2-yl)boronic acid supplier Ordinarily, it takes about 1 decades for theAbbreviations: AMP, adenosine monophosphate; AMPK, adenosine monophosphateactivated protein kinase; ATP, adenosine triphosphate; BMJ, bitter melon juice; ERK, extracellular signalregulated kinase; IHC, immunohistochemistry; MTT, 3(4,5dimethylthiazole2yl)two,5diphenyl tetrazolium bromide; MS, mass spectrometry; PCNA, proliferating cell nuclear antigen; ROS, reactive oxygen species; TUNEL, terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nickend labeling; XIAP, Xlinked inhibitor of apoptosis protein.1363404-84-5 Chemscene development of clinically defined `pancreatic cancer’, but symptoms are not obvious till the late stage in the disease.PMID:24202965 Thus, pancreatic cancer is generally termed as a `silent killer’. Final year alone, 44 030 new instances of pancreatic cancer have been reported within the USA, with 37 660 connected deaths (1). Gemcitabine may be the frontline chemotherapeutic therapy in pancreatic cancer patients, however the remedial and survival rewards of chemotherapy alone or in mixture with other therapies are exceptionally low as the med.