Journal article
Effects of Thymoquinone in the Expression of Mucin 4 in Pancreatic Cancer Cells: Implications for the Development of Novel Cancer Therapies
Molecular cancer therapeutics, v 9(5), pp 1419-1431
01 May 2010
PMID: 20423995
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Pancreatic cancer is one of the most lethal cancers in the world, as it continues to be resistant to any therapeutic approaches. The high molecular weight glycoprotein mucin 4 (MUC4) is aberrantly expressed in pancreatic cancer and contributes to the regulation of differentiation, proliferation, metastasis, and the chemoresistance of pancreatic cancer cells. The absence of its expression in the normal pancreatic ductal cells makes MUC4 a promising target for novel cancer therapeutics. Natural products have been widely investigated as potential candidates in cancer therapies, and thymoquinone (TQ), extracted from the seeds of Nigella sativa, has shown excellent antineoplastic properties in some systems. In the present study, we evaluated the effect of TQ on pancreatic cancer cells and specifically investigated its effect on MUC4 expression. The MUC4-expressing pancreatic cancer cells FG/COLO357 and CD18/HPAF were incubated with TQ, and in vitro functional assays were done. The results obtained indicate that treatment with TQ downregulated MUC4 expression through the proteasomal pathway and induced apoptosis in pancreatic cancer cells by the activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways. In agreement with previous studies, the decrease in MUC4 expression correlated with an increase in apoptosis, decreased motility, and decreased migration of pancreatic cancer cells. MUC4 transient silencing studies showed that c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways are activated in pancreatic cancer cells, indicating that the activation of these pathways by TQ is directly related to the MUC4 downregulation induced by the drug. Overall, TQ has potential for the development of novel therapies against pancreatic cancer. Mol Cancer Ther; 9(5); 1419-31. (C) 2010 AACR.
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Details
- Title
- Effects of Thymoquinone in the Expression of Mucin 4 in Pancreatic Cancer Cells: Implications for the Development of Novel Cancer Therapies
- Creators
- Maria P. Torres - Thomas Jefferson UniversityMoorthy P. Ponnusamy - Thomas Jefferson UniversitySubhankar Chakraborty - Thomas Jefferson UniversityLynette M. Smith - Thomas Jefferson UniversitySrustidhar Das - Thomas Jefferson UniversityHwyda A. Arafat - Thomas Jefferson UniversitySurinder K. Batra - Thomas Jefferson University
- Publication Details
- Molecular cancer therapeutics, v 9(5), pp 1419-1431
- Publisher
- American Association of Cancer Research
- Number of pages
- 13
- Grant note
- CA78590; CA111294; CA133774; CA131944 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA U01CA111294 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000278487500034
- Scopus ID
- 2-s2.0-77952140698
- Other Identifier
- 991022047145604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology