TY - JOUR AB - Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front‑line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcitabine‑resistant (GR) and gemcitabine‑sensitive (GS) PanC cells and underlying molecular mechanisms, together with efficacy of a natural agent bitter melon juice (BMJ). GR PanC cells showed distinct morphological features including spindle‑shaped morphology and a decrease in E‑cadherin expression. GR cells also showed higher ATP production with an increase in oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Molecular studies showed higher expression of glucose transporters (GLUT1 and 4) suggesting an increase in glucose uptake by GR cells. Importantly, GR cells showed a significant increase in Akt and ERK1/2 phosphorylation and their inhibition decreased cell viability, suggesting their role in survival and drug resistance of these cells. Recently, we reported strong efficacy of BMJ against a panel of GS cells in culture and nude mice, which we expanded here and found that BMJ was also effective in decreasing both Akt and ERK1/2 phosphorylation and viability of GR PanC cells. Overall, we have identified novel mechanisms of gemcitabine resistance in PanC cells which are targeted by BMJ. Considering the short survival in PanC patients, our findings could have high translational potential in controlling this deadly malignancy. AD - Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA AU - Somasagara,Ranganatha,R. AU - Deep,Gagan AU - Shrotriya,Sangeeta AU - Patel,Manisha AU - Agarwal,Chapla AU - Agarwal,Rajesh DA - 2015/04/01 DO - 10.3892/ijo.2015.2885 EP - 1857 IS - 4 JO - Int J Oncol KW - pancreatic cancer bitter melon juice natural products PY - 2015 SN - 1019-6439 1791-2423 SP - 1849 ST - Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells T2 - International Journal of Oncology TI - Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells UR - https://doi.org/10.3892/ijo.2015.2885 VL - 46 ER -