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Article

The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer

  • Authors:
    • Arvind Thakkar
    • Dhruvitkumar Sutaria
    • B. Karthik Grandhi
    • Jeffrey Wang
    • Sunil Prabhu
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA
  • Pages: 1671-1677
    |
    Published online on: February 5, 2013
       https://doi.org/10.3892/or.2013.2276
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Abstract

Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with ~37,000 deaths each year. The present study evaluated the chemopreventive potential of a combination of aspirin (ASP), curcumin (CUR) and sulforaphane (SFN) in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Results demonstrated that low doses of ASP (1 mM), CUR (10 µM) and SFN (5 µM) (ACS) combination reduced cell viability by ~70% (P<0.001), and also induced cell apoptosis by ~51% (P<0.001) accompanied by activation of caspase-3 and Poly(ADP-ribose) polymerase (PARP) proteins. The NF-κB DNA binding activity was inhi­bited by ~45% (P<0.01) and ~75% (P<0.001) in MIA PaCa-2 and Panc-1 cells, respectively. Mechanistic studies revealed that ACS promoted increase expression of phospho extracellular signal-regulated kinase 1/2 (P-ERK1/2), c-Jun, p38 MAPK and p53 proteins. Furthermore, the cells pretreated with U0126 (ERK1/2 inhibitor) partially abolished the effect of ACS on cell viability. Data from this study demonstrate that a low-dose ACS combination inhibits cell growth by inducing cell apoptosis, and proposes sustained activation of the ERK1/2 signaling pathway as one of the possible mechanisms.
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Copy and paste a formatted citation
Spandidos Publications style
Thakkar A, Sutaria D, Grandhi BK, Wang J and Prabhu S: The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer. Oncol Rep 29: 1671-1677, 2013.
APA
Thakkar, A., Sutaria, D., Grandhi, B.K., Wang, J., & Prabhu, S. (2013). The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer. Oncology Reports, 29, 1671-1677. https://doi.org/10.3892/or.2013.2276
MLA
Thakkar, A., Sutaria, D., Grandhi, B. K., Wang, J., Prabhu, S."The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer". Oncology Reports 29.4 (2013): 1671-1677.
Chicago
Thakkar, A., Sutaria, D., Grandhi, B. K., Wang, J., Prabhu, S."The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer". Oncology Reports 29, no. 4 (2013): 1671-1677. https://doi.org/10.3892/or.2013.2276
Copy and paste a formatted citation
x
Spandidos Publications style
Thakkar A, Sutaria D, Grandhi BK, Wang J and Prabhu S: The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer. Oncol Rep 29: 1671-1677, 2013.
APA
Thakkar, A., Sutaria, D., Grandhi, B.K., Wang, J., & Prabhu, S. (2013). The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer. Oncology Reports, 29, 1671-1677. https://doi.org/10.3892/or.2013.2276
MLA
Thakkar, A., Sutaria, D., Grandhi, B. K., Wang, J., Prabhu, S."The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer". Oncology Reports 29.4 (2013): 1671-1677.
Chicago
Thakkar, A., Sutaria, D., Grandhi, B. K., Wang, J., Prabhu, S."The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer". Oncology Reports 29, no. 4 (2013): 1671-1677. https://doi.org/10.3892/or.2013.2276
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