Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells

  • Authors:
    • Ranganatha R. Somasagara
    • Gagan Deep
    • Sangeeta Shrotriya
    • Manisha Patel
    • Chapla Agarwal
    • Rajesh Agarwal
  • View Affiliations

  • Published online on: February 9, 2015     https://doi.org/10.3892/ijo.2015.2885
  • Pages: 1849-1857
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Abstract

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.
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April-2015
Volume 46 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Somasagara RR, Deep G, Shrotriya S, Patel M, Agarwal C and Agarwal R: Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells. Int J Oncol 46: 1849-1857, 2015.
APA
Somasagara, R.R., Deep, G., Shrotriya, S., Patel, M., Agarwal, C., & Agarwal, R. (2015). Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells. International Journal of Oncology, 46, 1849-1857. https://doi.org/10.3892/ijo.2015.2885
MLA
Somasagara, R. R., Deep, G., Shrotriya, S., Patel, M., Agarwal, C., Agarwal, R."Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells". International Journal of Oncology 46.4 (2015): 1849-1857.
Chicago
Somasagara, R. R., Deep, G., Shrotriya, S., Patel, M., Agarwal, C., Agarwal, R."Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells". International Journal of Oncology 46, no. 4 (2015): 1849-1857. https://doi.org/10.3892/ijo.2015.2885