Abstract
Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models.
Highlights
Over the past several decades, research on the action of plant bioactive constituents has been focused predominantly on their benefits for human health
We have mainly summarized the effects of phenethyl isothiocyanate (PEITC), sulforaphane (SFN), benzyl isothiocyanate (BITC) and allyl isothiocyanate (AITC) in prostate cancer (PCa) among the different compounds derived from the hydrolysis of glucosinolates (Table 1)
This effect is extensible to the PEITC metabolite, PEITC-NAC (N-acetylcysteine conjugate of phenethyl isothiocyanate), which is produced as a result of absorption and metabolism in humans by conjugation of glutathione followed by conversion via the mercapturic acid pathway to a NAC
Summary
Over the past several decades, research on the action of plant bioactive constituents has been focused predominantly on their benefits for human health. The family Brassicaceae is a large group, having about 3000 species in 350 genera, including several types of edible plants, which are sometimes referred to as ‘the cabbage family’. Glucosinolates undergo hydrolysis by myrosinase to yield glucose, sulfate and aglucones that can undergo fragmentation and/or molecular rearrangement This process will yield isothiocyanates (ITCs), thiocyanates, oxazolindine-2-thione and nitriles, depending on the specific glucosinolate substrate, myrosinase isozyme, reaction pH and the presence of certain ions and the activity of specific protein factors, such as the epithiospecifier protein (ESP) [6]. Most of the protective activities of glucosinolates, among them that one against cancer, can be attributed to their hydrolytic products, of which the ITCs are prominent examples [7,8,9] For this reason there is an increase in their value as therapeutic compounds to be used in medicine and their value as food supplements for human diet [10]
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