Prostate cancer chemopreventive activity of phenethyl isothiocyanate through epigenetic regulation (Review)

Abstract

Abstract. Prostate cancer is one of the most commonly diagnosed cancers in men. The number of affected men is expected to rapidly increase as the population of males over the age of 50 grows worldwide. For patients who are not cured by local treatment and experience metastatic disease, neither androgen ablation nor chemotherapy can abrogate progression and death from androgen-independent/hormonerefractory disease. Therefore, finding strategies for the prevention of prostate cancer initiation and disease progression is a medical challenge. Consumption of cruciferous vegetables has been reported to be associated with reduced incidence of prostate cancer cases. The isothiocyanates, including phenethyl isothiocyanate (PEITC), from cruciferous vegetables have been demonstrated as active components responsible for chemoprevention. In this review, we summarize the recent findings of PEITC on prostate cancer prevention with an emphasis on epigenetic mechanisms. Studies have indicated that PEITC mediates gene regulation, such as downregulation of androgen receptor expression and induction of endogenous cyclin-dependent kinase inhibitors, p21 and p27. The gene for detoxifying enzyme π-class glutathione S-transferase (GSTP1), silenced in the vast majority of prostate tumor cells, could be reactivated and the enzymatic function recovered. This may be through epigenetic mechanisms as PEITC is a dual inhibitor of histone deacetylases and aberrant CpG island methylation of various genes. The epigenetic regulation may play a critical role, along with interactive mechanisms including the disruption of microtubule polymerization, in prostate cancer prevention by PEITC. These mechanisms target and correct the aberrations fundamental to the initiation and progression of carcinogenesis in cells, and restoring the cells to a more normal state. Inhibiting and eliminating cancer cells forms the basis of cancer prevention. Contents Introduction 2. Consumption of Brassica vegetables reduces prostatecancer risk 3. Downregulation of AR expression by PEITC through epigenetic mechanisms 4. Restoration of GSTP1 expression by PEITC via CpG island demethylation 5. PEITC inhibits prostate tumors and CGI methylation of the MGMT gene in TRAMP mice 6. Induction of endogenous cdk inhibitors by PEITC 7. Summary and conclusions IntroductionProstate cancer is the most commonly diagnosed cancer in men in the US. There were an expected 192,280 new cases and 27,360 deaths from prostate cancer in 2009 (1). Prostate cancer is usually found in elderly men. The prevalence of prostatic intraepithelial neoplasia and proliferative inflammatory atrophy, which are believed to be precursors of prostate cancers, may have a long latency period of ten or more years before developing into invasive carcinomas (2,3). Such factors lend credence to the growing belief that any delay in the time course of neoplastic development, achieved through pharmacological, hormonal and nutritional intervention, could result in a substantial reduction in the incidence of tumors. Even a ...

Recent advances in understanding the role of diet and obesity in the development of colorectal cancer

“…The biological activity of glucosinolates from brassicas in relation to cancer have been extensively reviewed (128,129) , and include induction of drug metabolising enzymes and endogenous anti-oxidants, cell cycle arrest and induction of apoptosis (130,131) . There is also evidence that the isothiocyanate metabolites of glucosinolates can have epigenetic effects through changes in histone acetylation and protection against aberrant CGI methylation in a potentially beneficial manner (132)(133)(134) . Furthermore, it has recently been reported that one glucosinolate derivative, 3,3 0 -diindolylmethane, can modify inflammation in an animal model of colitis (135) .…”

Apoptotic death in curcumin-treated NPC-TW 076 human nasopharyngeal carcinoma cells is mediated through the ROS, mitochondrial depolarization and caspase-3-dependent signaling responses

“…NPC-TW 076 cells at density of 2x10 5 cells/well were placed on 12-well plates and exposed to 10 µM curcumin, or only with vehicle (DMSO, 1% in culture media), and then cells were incubated for 6, 12, 24 and 48 h. After incubation, cells from each treatment were individually harvested by brief trypsinization then washed twice, and then PBS containing 40 µg/ml PI, 0.1 mg/ ml RNase and 0.1% Triton X-100 was added for 30 min at 37˚C and left in the dark. The PI stained cells were analyzed for quantification, cell cycle distribution and sub-G1 phase (apoptosis) by flow cytometry (28,29).…”

“…NPC-TW 076 cells (2x10 5 ) on 12-well plates were incubated with 10 µM curcumin for 0, 24 and 48 h. Cells from each well were harvested and washed twice with PBS, then substrates were used (PhiPhiLux-G 1 D 2 for caspase-3, OncoImmunin, Inc.) and the activities of caspase-3 was determinated by flow cytometry as described previously (22,27).…”

“…Currently, the treatments of NPC are still problematic, and thus new therapeutic agents are required. Numerous studies have been tried to identify new naturally occurring chemopreventive or chemotherapy agents for using to inhibit cancer in vitro and in vivo (5)(6)(7).…”

Ethanolic extract of Brazilian green propolis sensitizes prostate cancer cells to TRAIL-induced apoptosis

“…Natural products have been utilized in cancer prevention because of their ability to induce apoptosis (59,60). The role of dietary products in the prevention of prostate cancer has been confirmed in numerous preclinical and epidemiological studies (57,(61)(62)(63). Dietary agents derived from a natural source are considered pharmacologically safe and have potential use in cancer chemoprevention (3).…”