Isothiocyanates from cruciferous vegetables have been studied extensively in cells and in animals for their disease preventive and therapeutic effects. However, translating their utility to human populations has been both limited and challenging. Herein, clinical trials employing two isothiocyanates, sulforaphane (SFN; 1-isothiocyanato-4-(methylsulfinyl) butane) and phenethyl isothiocyanate (PEITC; 2-isothiocyanatoethylbenzene) that are isolated principally from broccoli and watercress, respectively, are summarized and discussed. Both of these compounds have been used in small human clinical trials, either within food matrices or as single agents, against a variety of diseases ranging from cancer to autism. Results suggest an opportunity to incorporate them, or more likely preparations derived from their source plants, into larger human disease mitigation efforts. The context for the applications of these compounds and plants in evidence-based food and nutritional policy is also evaluated.

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With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate produced by cruciferous vegetables such as broccoli, is found to be a highly promising chemoprevention agent against not only variety of cancers such as breast, prostate, colon, skin, lung, stomach or bladder carcinogenesis, but also cardiovascular disease, neurodegenerative diseases, and diabetes. For reasons of experimental exigency, pre-clinical studies have focused principally on sulforaphane itself, while clinical studies have relied on broccoli sprout preparations rich in either sulforaphane or its biogenic precursor, glucoraphanin. Substantive subsequent evaluation of sulforaphane pharmacokinetics and pharmacodynamics has been undertaken using either pure compound or food matrices. Sulforaphane affects multiple targets in cells. One key molecular mechanism of action for sulforaphane entails activation of the Nrf2-Keap1 signaling pathway although other actions contribute to the broad spectrum of efficacy in different animal models. This review summarizes the current status of pre-clinical chemoprevention studies with sulforaphane and highlights the progress and challenges for the application of foods rich in sulforaphane and/or glucoraphanin in the arena of clinical chemoprevention.

Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models. The goals of this study are to evaluate withanolides such as WA as well as Withania somnifera root extract as inducers of Nrf2 signaling, to probe the underlying signaling mechanism of WA and to determine whether prevention of acetaminophen (APAP)-induced hepatic toxicity in mice by WA occurs in an Nrf2-dependent manner. We observed that WA profoundly protects wild-type mice but not Nrf2-disrupted mice against APAP hepatotoxicity. WA is a potent inducer of Nrf2-dependent cytoprotective enzyme expression both in vivo and in vitro. Unexpectedly, WA induces Nrf2 signaling at least in part, in a Keap1-independent, Pten/Pi3k/Akt-dependent manner in comparison to prototypical Nrf2 inducers, sulforaphane and CDDO-Im. The identification of WA as an Nrf2 inducer that can signal through a non-canonical, Keap1-independent pathway provides an opportunity to evaluate the role of other regulatory partners of Nrf2 in the dietary and pharmacological induction of Nrf2-mediated cytoprotection.

The identification of bioactive molecules that have potential to interrupt carcinogenesis continues to garner research interest. In particular, molecules that have dietary origin are most attractive because of their safety, cost-effectiveness and feasibility of oral administration. Nutraceuticals have played an important role in the overall well-being of humans for many years, with or without rigorous evidence backing their health claims. Traditional medicine systems around the world have utilized plants for millennia that have medicinal properties, providing an opportunity for modern day researchers to assess their efficacies against ailments such as cancer. Withania somnifera (WS) is a plant that has been used in Ayurveda (an ancient form of medicine in Asia) and in the recent past, has been demonstrated to have anti-tumorigenic properties in experimental models. While scientific research performed on WS has exploded in the past decade, much regarding the mode of action and molecular targets involved remains unknown. In this review, we discuss the traditional uses of the plant, the experimental evidence supporting its chemopreventive potential as well as roadblocks that need to be overcome in order for WS to be evaluated as a chemopreventive agent in humans.