Department of Cancer Biology
Member, Center for Epigenetics and Stem Cell Biology
Ph.D., University of Calcutta, India, 1982
Postdoctoral, University of Puerto Rico School of Medicine, San Juan, 1986-1988
Postdoctoral, University of Missouri-Columbia School of Medicine, 1988-1990
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 a novel strategy. 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 research is to determine 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 research is specifically looking at histone deacetylase 1 (HDAC1), which is upregulated in pancreatic cancers. The research 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, these studies will give us the preclinical data essential for moving towards clinical trials.
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
Dhar, A., Ray, A. The CCN family proteins in carcinogenesis. Experimental Oncology 32:2-9, 2010.
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, 2011.
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 301:G929-G937, 2011.
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. 10:2146-2156, 2011.
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 13:173-179, 2012.
Animesh Dhar, Ph.D.
Department of Cancer Biology