I am interested in developing novel mechanism-based dietary agents for prevention and treatment of cancer.
According to American Cancer Society, cancer is the second most common cause of death in the United States. While women have slightly more than 1 in 3 lifetime risk of developing cancer, men have approximately 1 in 2, in the US.
The two important characteristics of cancer are uncontrolled cell growth and spread of abnormal cells. Highly proliferating cancer cells require continuous supply of lipids for energy and cell membrane production. The key enzyme that catalyzes de novo synthesis of fatty acids is FASN (fatty acid synthase).
FASN is overexpressed in many human cancers including the three most common cancers in the US, i.e., breast, prostate, and lung cancer. Overexpression of this enzyme is associated with poor prognosis indicating that FASN could be a great target to inhibit cancer.
Previous research has found that synthetic FASN inhibitors can effectively suppress several different types of cancer. In the immediate future, my plans include targeting abnormal metabolic pathways of cancer including fatty acid synthesis pathway using natural dietary agents, such as lupeol, resveratrol, and fisetin.
Many fruits and vegetables contain biologically active chemicals that are beneficial for health. Recently, prevention of cancer through natural dietary agents has received an increasing interest since these “nutraceuticals” exert their anti-cancer effects by targeting multiple signaling pathways that are specific to cancer. My long-term goals will be focused on identifying new molecular targets of phytochemicals for cancer chemoprevention.
PUBLISHED SCIENTIFIC ARTICLES (denotes undergraduates as co-authors)
Suh, Y., Kasza, I., Wollny, D., Clark, R., Roopra, A., Coleman, R., Yen, M., Nelson, D., Yen, E., and Alexander,
C.M. (2014) Syndecan-1 is required to maintain intradermal fat and prevent cold stress. PLOS Genetics 10, e1004514.
Khan, N., Afaq, F., Khusro, F.H., Adhami, V.M., Suh, Y., and Mukhtar, H. (2012) Dual inhibition of phosphatidylinositol 3-kinase/AKT and mammalian target of rapamycin signaling in human nonsmall cell lung cancer cells by a dietary flavonoid fisetin. International Journal of Cancer 130, 1695-705.
Johnson, J.J., Syed, D.N., Suh, Y., Heren, C.R., Saleem, M., Siddiqui, I.A., and Mukhtar, H. (2010) Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention. Cancer Prevention Research 3, 1112-23.
Suh, Y., Afaq, F., Khan, N., Johnson, J.J., Khusro, F.H., and Mukhtar, H. (2010) Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells. Carcinogenesis 31, 1424-33.
Saleem, M., Murtaza, I., Tarapore, R.S., Suh, Y., Adhami, V.M., Johnson, J.J., Siddiqui, I.A., Khan, N., Asim, M., Hafeez, B.B., Shekhani, M.T., Li, B., and Mukhtar, H. (2009) Lupeol inhibits proliferation of human prostate cancer cells by targeting beta-catenin signaling. Carcinogenesis 30, 808-17.
Suh, Y., Afaq, F., Johnson, J.J., and Mukhtar, H. (2009) A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-κB signaling pathways. Carcinogenesis 30, 300-7.
Johnson, J.J., Syed, D.N., Heren, C.R., Suh, Y., Adhami, V.M., and Mukhtar, H. (2008) Carnosol, a Dietary Diterpene, Displays Growth Inhibitory Effects in Human Prostate Cancer PC3 Cells Leading to G(2)-Phase Cell Cycle Arrest and Targets the 5′-AMP-Activated Protein Kinase (AMPK) Pathway. Pharm. Res. 25, 2125-2134.
Syed, D.N., Suh, Y., Afaq, F., and Mukhtar, H. (2008) Dietary agents for chemoprevention of prostate cancer. Cancer Lett. 265, 167-176.
Saleem, M., Maddodi, N., Abu Zaid, M., Khan, N., Bin Hafeez, B., Asim, M., Suh. Y, Yun, J.M., Setaluri, V., and Mukhtar, H. (2008) Lupeol inhibits growth of highly aggressive human metastatic melanoma cells in vitro and in vivo by inducing apoptosis. Clin. Cancer Res. 14, 2119-2127.
Sahab, Z.J., Suh, Y., and Sang, Q.X. (2005) Isoelectric-point based prefractionation of proteins from crude biological samples prior to two-dimensional gel electrophoresis. J. Proteome Res. 4, 2266-2272.
Kang, T., Park, H.I., Suh, Y., Zhao, Y.G., Tschesche, H. and Sang, Q.X. (2002) Autolytic processing at Glu586- Ser587 within the cysteine-rich domain of human adamalysin 19/disintegrin-metalloproteinase 19 is necessary for its proteolytic activity. J. Biol. Chem. 277, 48514-48522.