@article {Somasagara:2015:1019-6439:1849,
title = "Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells",
journal = "International Journal of Oncology",
parent_itemid = "infobike://sp/ijo",
publishercode ="sp",
year = "2015",
volume = "46",
number = "4",
publication date ="2015-01-01T00:00:00",
pages = "1849-1857",
itemtype = "ARTICLE",
issn = "1019-6439",
eissn = "1791-2423",
url = "https://www.ingentaconnect.com/content/sp/ijo/2015/00000046/00000004/art00047",
doi = "doi:10.3892/ijo.2015.2885",
author = "Somasagara and Deep and Shrotriya and Patel and Agarwal and Agarwal",
abstract = "Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the frontline 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 gemcitabineresistant (GR) and gemcitabinesensitive (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 spindleshaped morphology and a decrease in Ecadherin 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 (GLUT1and4) 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.",
}