Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via Sp1 and androgen receptor down‐regulation

Beklemisheva, A.; Feng, Jing; Yeh, Yunshin; Wang, L. G.; Chiao, Jen Wei

doi:10.1002/pros.20472

Cited by 15 publications

(19 citation statements)

References 27 publications

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“…Even though we observed a consistent decrease in AR mRNA and CBP in a large number of PTC, FTC and FTA tissues from males and females, Pearson's correlation analysis did not show any statistically significant correlation between the two. Inhibition of Sp1 activity reduces AR expression in LNCaP cell line [77] and in rat prostate [78]. Therefore, decreased Sp1 in PTC, FTC and FTA tissues from women and the significant positive correlation observed between AR mRNA and Sp1 expression pattern in PTC and FTA tissues from women suggest that Sp1 could contribute to the down-regulation of AR in a majority of thyroid tumors in females.…”

Section: Discussionmentioning

confidence: 69%

Androgen receptor expression in human thyroid cancer tissues: A potential mechanism underlying the gender bias in the incidence of thyroid cancers

Stanley

Aruldhas

Chandrasekaran

et al. 2012

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 69%

Androgen receptor expression in human thyroid cancer tissues: A potential mechanism underlying the gender bias in the incidence of thyroid cancers

Stanley

Aruldhas

Chandrasekaran

et al. 2012

The Journal of Steroid Biochemistry and Molecular Biology

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“…In the model of testosterone (hormone)-induced prostatic cell growth, PEITC negated the growth via downregulation of androgen receptor (AR) (81). This repression of AR in prostate cancer cells by PEITC is significant in cancer chemoprevention since abnormalities of the AR, such as overexpression, have been postulated to be related to the hormone-independent growth of prostate cancer (81). The question as to how PEITC regulates AR was subsequently investigated.…”

Section: Receptors As Molecular Targets For Peitc and Sfnmentioning

confidence: 99%

“…The question as to how PEITC regulates AR was subsequently investigated. It was found that PEITC mediates dual effects on AR, both at the transcriptional and the post-translational level (81). At the transcriptional level, the AR transcript level was reduced via inhibition of the transcription factor Sp1 (which transactivates AR promoter), and at the post-translational level, AR protein degradation was accelerated (81).…”

Section: Receptors As Molecular Targets For Peitc and Sfnmentioning

confidence: 99%

“…It was found that PEITC mediates dual effects on AR, both at the transcriptional and the post-translational level (81). At the transcriptional level, the AR transcript level was reduced via inhibition of the transcription factor Sp1 (which transactivates AR promoter), and at the post-translational level, AR protein degradation was accelerated (81). Correspondingly, there is a report suggesting that SFN regulates the expression of estrogen receptor alpha (ERα) in human breast cancer cells (82).…”

Section: Receptors As Molecular Targets For Peitc and Sfnmentioning

confidence: 99%

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Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

Cheung

Kong

2009

AAPS J

324

289

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Abstract. Development of cancer is a long-term and multistep process which comprises initiation, progression, and promotion stages of carcinogenesis. Conceivably, it can be targeted and interrupted along these different stages. In this context, many naturally occurring dietary compounds from our daily consumption of fruits and vegetables have been shown to possess cancer preventive effects. Phenethyl isothiocyanate (PEITC) and sulforaphane (SFN) are two of the most widely investigated isothiocyanates from the crucifers. Both have been found to be very potent chemopreventive agents in numerous animal carcinogenesis models as well as cell culture models. They exert their chemopreventive effects through regulation of diverse molecular mechanisms. In this review, we will discuss the molecular targets of PEITC and SFN potentially involved in cancer chemoprevention. These include the regulation of drugmetabolizing enzymes phase I cytochrome P450s and phase II metabolizing enzymes. In addition, the signaling pathways including Nrf2-Keap 1, anti-inflammatory NFκB, apoptosis, and cell cycle arrest as well as some receptors will also be discussed. Furthermore, we will also discuss the similarities and their potential differences in the regulation of these molecular targets by PEITC and SFN.

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“…In the testosterone-primed prostates, cellular proliferation was stimulated with a significant increase in the cyclins D1 and E, cdk2 and a decrease in p27. Concomitantly, Rb was inactivated as shown by an increase in Rb phosphorylation (54). Inactivation of Rb leads to enhanced activity of E2F1, thereby activating downstream target DNMT1 transcription.…”

Section: Peitc Inhibits Prostate Tumors and Cgi Methylation Of The Mgmentioning

confidence: 99%

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

Wang¹

2010

Int J Oncol

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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 ...

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Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via Sp1 and androgen receptor down‐regulation

Abstract: PEITC modulates the testosterone-influenced growth by repressing Sp1, thus down-regulating AR and proliferation. PEITC from cruciferous vegetables may represent a regulator for hormone-dependent growth of the prostate.

Cited by 15 publications

References 27 publications

Androgen receptor expression in human thyroid cancer tissues: A potential mechanism underlying the gender bias in the incidence of thyroid cancers

Androgen receptor expression in human thyroid cancer tissues: A potential mechanism underlying the gender bias in the incidence of thyroid cancers

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

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

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