257P - Molecular mechanisms involved in the synergistic interaction of novel formulated curcumin with gemcitabine in pancreatic cancer cells

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Pancreatic Cancer
Presenter amir Avan
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors A. Avan1, S. Shahidsales2, F. Ghasemi3, S. Ahmadi-Simab4, R. Mahdavian Zadeh5, A. Sahebkar6
  • 1Department Of Modern Sciences And Technologies, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, 000000 - Mashhad/IR
  • 2Radiotherapy Oncology, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, 000000 - Mashhad/IR
  • 3Department Of Modern Sciences And Technologies, Mashhad University of Medical Sciences, 0000000000 - Mashhad/IR
  • 4Cancer Research Center, Mashhad University of Medical Sciences-Omid Hospital Cancer Research Center, 000000000 - Mashhad/IR
  • 5Department Of Medical Biotechnology, Mashhad University of Medical Sciences, 0000000000 - Mashhad/IR
  • 6Biotechnology Research Center, Mashhad University of Medical Sciences, 0000000000 - Mashhad/IR

Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer related death. Despite extensive efforts, the poor prognosis of this disease has not improved over the past decades. Thus, there is an urgent need to develop novel anticancer agents that either exert a better efficacy than gemcitabine or improve gemcitabine activity in the context of combinatorial regimens. Against this background, the anticancer activity of curcumin has been investigated in different tumor types. Here we explored the molecular mechanism underlying the antitumor effect of four novel forms of curcumin (phytosomal) alone or in combination with gemcitabine in PDAC

Methods

The viability of MIAPaCa-2, PANC-1 and PANC-2 cells was determined using MTT assay as well as in 3 dimensional cell culture model. We performed migration and invasion assays in the cells, while the perturbation of cell cycle was assessed by FACS before and after therapy

Results

Curcumin inhibited PDAC cell growth with IC50 of 100 nM in MiaPaCa-2, and synergistically enhanced the antiproliferative activity of gemcitabine and pro-apoptotic activity of gemcitabine. We then explored the cytotoxic activities of three formulated forms of curcumin (phospholipidated curcumin, amorphous curcumin and turmeric oleoresin) in the cells. The results revealed that the cell growth inhibition was more pronounced with amorphous curcumin. Moreover curcumin decreased cell migration/invasion, which was associated with increased E-cadherin and reduced MMP9 expression. Curcumin mediated tumor shrinkage in spheroid model, enhanced the percentages of cells in S-phase, and significantly increased apoptosis. Moreover, curcumin suppressed Wnt pathway via modulation of survivin, and CyclinD1

Conclusions

Our data provide novel insights into the ability of curcumin to interfere with cell-proliferation, induce apoptosis, reduce migration/invasion and synergistically interact with gemcitabine in PDAC cells, supporting further studies on the therapeutic potential of this agent in treatment of pancreatic cancer

Clinical trial indentification

Legal entity responsible for the study

N/A

Funding

Mashhad University of Medical Sciences

Disclosure

All authors have declared no conflicts of interest.