Animesh Dhar, PhD
Adjunct faculty, Department of Molecular & Integrative Physiology
Ph.D.:1982, University of Calcutta, India
Postdoctoral: 1986 -1988, University of Puerto Rico School of Medicine, San Juan
Postdoctoral: 1988- 1990, University of Missouri-Columbia School of Medicine
Pancreatic cancer is one of the most lethal malignancies. There are no effective treatments available for this debilitating disease. Recent data from the NCI estimated that in 2010, more than 43,000 individuals in the US would have been diagnosed with pancreatic cancer, and 36,800 would have died from the disease. In fact, the rate of mortality from pancreatic cancers has significantly increased when compared to other cancers. Current treatment paradigms, including surgery are not effective in controlling the disease. Part of the problem is that there are no symptoms early on during the progression of the disease, leading to locally advance or metastatic disease at time of diagnosis. At present, there is no effective treatment available for pancreatic cancer.
Prevention and treatment for pancreatic cancer using crocetin compound derived from saffron, a spice and food colorant present in the dry stigmas of the plant Crocus sativas L., could be novel strategies. Therefore, current studies related to developing a novel crocetin compound for therapeutic against pancreatic cancer is very exciting. In preliminary studies, it was demonstrated by this group that the crude crocetin mixture could suppress pancreatic tumor in animal model. More recently, our group made highly pure compound from the crocetin, crocetinic acid that is even more potent in inhibiting the tumor growth. Significant aspect of this proposal is determining whether crocetin-mediated anti-tumor activity occurs in part through affecting histone acetylation. Epigenetic events link alterations in chromatin structure with the development of cancer. Both histone hyperacetylation and hypoacetylation appear to be important in the neoplastic process. This proposal is specifically looking at histone deacetylase 1 (HDAC1), which is upregulated in pancreatic cancers. The grant is designed to further determine the molecular mechanisms underlying the activity of crocetinic acid, and also expand the preliminary observations determining whether the compound can inhibit metastatic disease. This is of high significance because it is a metastatic disease with poor prognosis, and inhibiting metastasis can significantly improve patient survival. More importantly, the studies proposed in the current application will give us the preclinical data essential for moving towards clinical trials.
Funding Source: NCI RO-1
- Helling, T.S., Edwards, C., Chang, C., Hodges, T., Helling, T.S. Jr., Dhar, A., and Van Way, C.W. Hepatic Apoptotic Activity Following Normothermic Inflow Occlusion and Reperfusion in the Swine Model. J. Surg. Res. 86:70-78, 1999.
- Chang, C., Dhar, A., Hahn, Y., Helling, T.S. Jr., and Van Way, C.W. The use of insulin and dextrose during resuscitation from hemorrhagic shock and increase hepatic ATP. J. Surg. Res. 92, 171, 2000.
- Van Way, C. W., Dhar, A., Morrison, D. C., Longoria, M. A. and Maxfield, D. M. Cellular Energetics in Hemorrhagic Shock. J. Trauma, 54, S169-S176, 2003
- Van Way, C. W., Dhar, A. and Morrison, D. Hemorrhagic shock: A new look at an old problem. Missouri Medicine, 100, 518, 2003.
- Dhar, A., Kujath, S., Van Way, C. W. Glutamine Administration during Total Parenteral Nutrition Protects Liver Adenosine Nucleotides during and after Subsequent Hemorrhagic Shock. J. Paren. Enter. Nutr. 27, 246-251, 2003.
- Helling, T. H., Dhar, A., Helling, T. S., Jr., Moore, T. B. and Van Way, C. W. Partial hepatectomy with or without endotoxin does not promote apoptosis in the rat liver. J. Surg. Res. 116, 1, 2004.
- Dhar, A., Cherian, G., Dhar, G., Ray, G., Sharma, G. and Banerjee, S. K. Molecular basis of protective effect of Crocetin on survival and liver tissue damage following hemorrhagic shock. Molecular and Cellular Biochemistry 278, 139 -146, 2005.
- Dhar, A., Mehta, S., Banerjee, S., Dhar, K., Dhar, G., Sengupta, K., Ray, G., Banerjee, S. K. and Campbell, D. R. Epidermal growth factor receptor, Is a novel therapeutic target for pancreatic cancer? Frontiers in Bioscience, 10, 1763-1767, 2005.
- Van Veldhuizen, P., Ray, G., Banerjee, S., Dhar, G., Kambhampati, S., Dhar, A. and Banerjee, S. K. 2-Methoxyestradiol modulates in prostate cancer cells: A possible mediator of 2-Methoxyestradiol-induced inhibition of cell growth. Int. J. Cancer, 122, 567-571, 2008 (PMC2837338).
- Dhar, A., Mehta, S., Dhar, G., K. Dhar, Banerjee, S., Campbell, D. R. and Banerjee, S. K. Crocetin inhibits Pancreatic Cancer Cell Proliferation and Tumor Progression in a Xenograft Mouse Model. Mol. Cancer Ther. 8, 315-323, 2009 (Journal Highlights).
- Ray, A. The CCN Family Proteins in Carcinogenesis. Experimental Oncology 32, 209, 2010.
- Dhar A. and Gutheil, W., Reed, G., Ray, A., Anant, S. and Dhar, A. Crocetin: a novel agent derived from saffron for prevention and therapy for cancer. Current Pharmaceutical Biotechnology (in press).
- Dhar, A., Fogt, L, Subramaniam, D. and Anant, S. Cancer stem cells: Novel target using dietary components for prevention and treatment. in Sarkar, F. Z (ed) Nutraceuticals and Cancer (in press).
- He, Z, Subramaniam, D, Ramalingam, S, Dhar, A, Postier, RG, Umar, S, Zhang, Y and Anant, S. Honokiol radiosensitizes colorectal cancer cells; enhanced activity in cells with mismatch repair defects. Am J Physiol Gastrointest Liver Physiol 2011 (Epub ahead of print).
- Subramaniam, D, Nicholes, ND, Dhar, A, Umar, S, Awasthi,V, Welch, DR, Jenson, RA and Anant, S. 3, 5-bis (2,4-difluorobenzylidene) - 4- piperidone, a novel compound that affects pancreatic cancer growth and angiogenesis. Mol Cancer Ther. 2011 (Epub ahead of print)
Dr. Shrikant Anant, Dr. Animesh Dhar and Dr Greg Reed at KUMC