The Singh laboratory is interested in preclinical and clinical development of novel agents, derived from dietary sources and traditional oriental and Indian medicinal plants, for prevention of prostate and breast cancer in humans.
The research interests of the Singh laboratory include preclinical and clinical development of novel cancer chemopreventive agents and rational design of combination chemoprevention regimens. Cellular and transgenic animal models are used to screen potential cancer chemopreventive constituents from dietary sources and traditional oriental and Indian medicinal plants. Cutting edge cellular, molecular biological, Omics, and imaging techniques are used to (a) determine the mechanism of action of promising cancer chemopreventive agents, (b) monitor effects on cancer progression, and (c) identify biomarkers of response potentially useful in future clinical trials.
Cancer chemoprevention is a relatively new but rapidly emerging sub-discipline in oncology and refers to the use of natural or synthetic agents to reverse or delay the process of carcinogenesis. Long latency of most epithelial cancers, including prostate and breast cancers, provides a large window of opportunity for intervention to prevent or slow disease progression. Accordingly, identification of agents that are relatively safe but can be used to prevent cancers is highly desirable to reduce disease-related cost, mortality, and morbidity for a large segment of population.
Epidemiological studies suggest that dietary intake of certain vegetables (e.g., cruciferous vegetables) may be protective against the risk of different types of cancers. The Singh laboratory has determined cancer chemopreventive efficacy of a few chemicals derived from edible plants, including watercress constituent phenethyl isothiocyanate (PEITC). The PEITC selectively inhibits OXPHOS in prostate cancer cells, but not in normal prostate epithelial cells, to trigger ROS-dependent apoptosis. Administration of PEITC in the diet (3 µmol PEITC/g diet) significantly decreases incidence as well as burden (affected area) of poorly differentiated prostate cancer in a transgenic mouse model (TRAMP mice) in association with induction of autophagy and overexpression of E-cadherin. Plasma proteomics reveals distinct changes in the expression of several proteins (eg, suppression of clusterin) in the PEITC-treated mice that could be used as biomarkers to assess PEITC response in future clinical trials.
Other ongoing projects in the Singh laboratory are focused on preclinical development of other natural products including garlic constituent diallyl trisulfide, broccoli constituent sulforaphane to name a few. One common yet unique characteristic of these natural products is that they selectively cause death of cancer cells.
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