research assistant professor
Ph.D., Chittaranjan National Cancer Institute,
Jadaupur University, Calcutta, India
Fields of Interest
Effect of dietary restriction on the growth of brain tumors.
I am seeking to define the molecular effects of total dietary restriction on brain tumor growth. Dietary restriction has documented beneficial effects on numerous diseases including cancer, yet its mechanism of action is unknown. Recently, we showed that dietary restriction has significant pro-apoptotic and anti-angiogenic effects on the inhibition of experimental brain tumor growth. Dietary restriction induced increase in apoptosis is associated with caspase-3 activation and PARP cleavage in brain tumors. Insulin like growth factor–1 (IGF-1) is a peripheral anti-apoptotic molecule, and is known to be influenced by dietary restriction. Therefore, we are interested to see whether or not dietary restriction influences ceramide levels and ceramide-linked regulatory proteins of apoptosis in brain tumors (i.e., if the IGF-1-ceramide-Fas-caspase signaling axis is the pathway influenced by dietary restriction).
My other project deals with anti-angiogenic effect of dietary restriction on brain tumors. We observed that dietary restriction significantly reduces micro-vessel density in tumors along with the reduction of serum vascular endothelial growth factor (VEGF), a major angiogenic cytokine. I am now focusing on the effects of dietary restriction on macrophage infiltration (TIMs) and angiogenic cytokine production in brain tumors. Recently, it was reported that IL-8 is induced in human glioma cells upon l igation of Fas. Therefore, Fas is not only an inducer of apoptosis, but also a mediator of angiogenesis in human brain tumors. Tumor cells may be protected from Fas-mediated apoptosis by the opposing angiogenic activity of IL-8 induced by Fas ligation. Macrophage inflammmatory protein (MIP-2), human homologue to IL-8, is one of the cytokines governed by Fas/CD95 pathway in gliomas and also influenced by caspases. Therefore, it will be interesting to see whether or not caloric stress can reduce the level of MIP-2.
Zuccoli, G., Marcello, N., Pisanello, A., Servadei, F., Vaccaro, S., Mukherjee, P., Seyfried, T.N. 2010. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report. Nutrition & Metabolism 7:33 (link to PubMed abstract).
Seyfried, T.N., Kiebish, M., Mukherjee, P., and Marsh, J. 2008. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets. Epilepsia 49 (8): 114–6 (link to PubMed abstract).
Marsh, J., Mukherjee, P., and Seyfried, T.N. 2008. Akt-dependent proapoptotic effects of dietary restriction on late-stage management of a phosphatase and tensin homologue/tuberous sclerosis complex 2-deficient mouse astrocytoma. Clinical Cancer Research 14(23): 7751–62 (link to PubMed abstract).
Mukherjee, P., Mulrooney, T.J., Marsh, J., Blair, D., Chiles, T.C., and Seyfried, T.N. 2008. Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain. Molecular Cancer 7: 37 (link to PubMed abstract).
Huysentruyt, L.C., Mukherjee, P., Banerjee, D., Shelton, L.M., and Seyfried, T.N. 2008. Metastatic cancer cells with macrophage properties: evidence from a new murine tumor model. International Journal of Cancer 123(1): 73–84.
Mukherjee, P., Faber, A.C., Shelton, L.M., Baek, R.C., Chiles, T.C., and Seyfried, T.N. 2008. Thematic review series: sphingolipids. Ganglioside GM3 suppresses the proangiogenic effects of vascular endothelial growth factor and ganglioside GD1a. Journal of Lipid Research 49(5): 929–938 (link to PubMed abstract).
Marsh, J., Mukherjee, P., Seyfried, T.N. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet. Nutrition & Metabolism 5: 33 (link to PubMed abstract).
Zhou, W., Mukherjee, P., Kiebish, M.A., Markis, W.T., Mantis, J.G., and Seyfried, T.N. 2007. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutrition & Metabolism 4: 5.
Abate, L.E., Mukherjee, P., and Seyfried, T.N. 2006. Gene-linked shift in ganglioside distribution influences growth and vascularity in a mouse astrocytoma. Journal of Neurochemistry 98(6): 1973–84 [Epub 2006, Aug 14].
Mukherjee, P., Abate, L.E., Seyfried, T.N. 2004. Antiangiogenic and proapoptotic effects of dietary restriction on experimental mouse and human brain tumors. Clinical Cancer Research 10: 5622–5629.
Seyfried., T.N., Sanderson, T.M., El-Abbadi, M.M., McGowan, R., and Mukherjee, P. 2003. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. British Journal of Cancer 89: 1375–1382 (link to PubMed abstract).
Mukherjee, P., El-Abbadi, M., Kasperzyk, J., Ranes, M. K., Seyfried, T. N. 2002. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse barin tumor model. British Journal of Cancer 86(10): 1615–21 (link to PubMed abstract).
Ranes, M. K., El-Abbadi, M., Manfredi, M.G., Mukherjee, P., Platt, F.M., Seyfried, T. N. 2001. N-butyldeoxynojirimycin reduces growth and ganglioside content of experimental mouse brain tumors. British Journal of Cancer 84(8): 1107–14 (link to PubMed abstract).
Mukherjee, P., Sotnikov, A.V., Manigan, H. J., Zhou, J., Blackburn, G.L., Visek, W.J., and Clinton, S.K. 1999. Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression. Journal of National Cancer Institute 91: 512–523 (link to PubMed abstract).
Mukherjee, P., Zhou, J., Sotnikov, A. V., and Clinton, S. K. 1999. Dietary and nutritional modulation of tumor angiogenesis. In: Antiangiogenic Agents in Cancer Therapy. Teicher, B.A, Ed. Humana Press, Totowa, N.J. pp. 237–262.
Zhou, J., Mukherjee, P., Grugger, E. T., Tanaka, T., Blackburn, G. L., and Clinton, S. K. 1998. The inhibition of bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis and angiogenesis. Cancer Research 58: 5231–5238 (link to PubMed abstract).
Mukhopadhyay, P., Sanyal, U., Chakrabarti, J., and Das, S. 1996. Inhibition of moloney virus induced leukemogenesis in mice by dietary restriction and supplemented soyabean. Cancer Journal 9: 41–46.
Mukhopadhyay, P., Bhattacharyya, J., Sanyal, U., and Das, S. 1995. Serum protein, lipid and selected vitamins during caloric restriction and soyabean supplementation in the diet of normal and tumor bearing mice. Nutrition Research 15: 983–992.
Mukhopadhyay, P., Dasgupta, J., Sanyal, U., and Das, S. 1994. Influence of dietary restriction and soyabean supplementation on groups of a murine lymphoma and host immune function. Cancer Letter 78: 151–157 (link to PubMed abstract).
Das, S., and Mukhopadhyay, P. 1994. Protease inhibitors in chemoprevention of cancer. An overview. Acta Oncologica 33: 859–865 (link to PubMed abstract).
Mukhopadhyay, P., Sarkar, R.N., and Dasgupta, J. 1992. Prevention and control of murine leukemia and lymphoma by soyabean supplemented diet. Indian Journal of Physiology & Allied Sciences 46: 178–185.