Foods/Supplements-Vitamins: Crucifero... - Advanced Prostate...

Advanced Prostate Cancer

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Foods/Supplements-Vitamins: Cruciferous Phytochemicals - [4] Phenethyl isothiocyanate [PEITC]

8 years ago•4 Replies

PEITC is a lesser-known cruciferus phytochemical than DIM or sulforaphane, but there heave been a substantial number of PCa studies.

The very brief PEITC Wiki-page [1] states:

"PEITC has been studied for its potential for chemoprevention of cancers, such as prostate cancer."

The richest source is watercress.

The inactive chemical in the intact leaf is gluconasturtiin. As with all of its glucosinolate cousins, the enzyme myrosinase is required, to cleave the glucose component & release the active element. I'm not sure that my teeth do a very efficient job, given that every cell has to be damaged in order to release all of the PEITC.

An alternative approach is to use a blender. When the myrosinase has been thoroughly liberated from a quantity of watercress, measure a daily dose of the puree into ice-cube tray compartments. Wrap & freeze. Remove a cube daily & allow to thaw before using.

Swanson has a "Full Spectrum Watercress" [2] (presumably marketing-speak for minimally processed). Who cares about the full spectrum? It's PEITC we need & the label promises nothing - merely 400 mg "whole herb". But at $3.99 for 60 caps it might be worth trying. If heat was involved duting production, the myrosinase will have been destroyed. Gluconasturtiin will not be affected, but it will be ineffective.

...

I suggest skimming through the study summaries below. Most of the studies will have terms that are unfamiliar. Rather than exclude them & end up with very little, I include them to indicate the level of interest in PEITC.

Interestingly, the studies are almost all American. No Pharma money to fund cruciferous studies, of course.

[3] (2017 - U.S.)

"Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model."

"PEITC administration to TRAMP mice ... resulted in a significant decrease in tumor expression of FASN {fatty acid synthase} protein. Consistent with these findings, the levels of total free fatty acids, total phospholipids, triglyceride, and ATP were significantly lower in the plasma and/or prostate tumors of PEITC-treated TRAMP mice compared with controls."

[4] Reactivation of epigenetically silenced genes; HDAC inhibition.

[4a] (2016 - U.S.) Epigenetic reactivation of RASSF1A.

"Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers."

"Collectively, the results of our study suggest that PEITC induces apoptosis in LNCaP cells potentially by reactivating RASSF1A via epigenetic mechanisms."

[4b] (2016 - U.S.)

"The glucosinolate-derived phenethyl isothiocyanate (PEITC) has been widely documented to reduce the risk of prostate cancer by modulating multiple biologically relevant processes. Emerging evidence suggests that PEITC may exert its anti-cancer effects through epigenetic mechanisms including microRNAs. Altered levels of miRNA have been linked to tumor malignancy due to their capacity to regulate functional gene expression in carcinogenesis."

"Our results indicate that miR-194 downregulates the expression of oncogenic MMP2 and MMP9 by targeting BMP1, which suggests a potential new mechanistic target by which PEITC suppresses prostate cancer cell invasiveness."

{The MMP family break down extracellular matrix - allowing cells to become mobile.}

[4c] (2014 - U.S.)

"Phenethyl isothiocyanate (PEITC), present naturally in cruciferous vegetables, is a chemopreventive agent. It blocks initiation and post-initiation progression of carcinogenesis. Mechanism study in human prostate cancer cells revealed that PEITC is a dual inhibitor of aberrant DNA hypermethylation and histone deacetylases, reactivating silenced genes and regulating the androgen-mediated growth of tumor cells. The identity of the cellular organelle that initially interacts with PEITC has not been fully described."

"Ultrastructural analyses have revealed condensed mitochondria and a perturbed mitochondrial cristae structure, which assumed a rounded and dilated shape within 4-hours of PEITC contact, and became more pronounced with longer PEITC exposure. ..."

"Mitochondria may represent the organelle target of the isothiocyanates, indicating that the isothiocyanates may be mitochondria-interacting agents to inhibit carcinogenesis."

[4d] (2010 - U.S. - Review)

"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 pi-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."

[4e] (2008 - U.S.)

"Natural isothiocyanates from cruciferous vegetables have been described as important dietary factors for prostate cancer prevention. Phenethyl isothiocyanate (PEITC), found rich in watercress, induces growth arrest and apoptosis in prostate cancer cells, and also inhibits the testosterone-mediated growth of prostates by regulating the androgen receptor and cell cycle progression in rats. PEITC has been recently identified as an inhibitor of histone deacetylases (HDACs). Herein we describe the mechanism of PEITC-mediated growth attenuation in relation to HDAC inhibition in human prostate cancer cells. Exposure of androgen-dependent prostate cancer cells LNCaP to PEITC resulted in cell cycle arrest and a p53-independent up-regulation of the inhibitors of cyclin-dependent kinases, including p21WAF1 and p27. The mechanism of p21 activation was investigated. PEITC significantly enhanced histone acetylation and induced selective modification of histone methylation for chromatin remodeling."

[4f] (2007 - U.S.)

"Prostate carcinoma is characterized by the silencing of pi-class glutathione S-transferase gene (GSTP1), which encodes a detoxifying enzyme. The silencing of GSTP1, due to aberrant methylation at the CpG island in the promoter/5'-UTR, occurs in the vast majority of prostate tumors and precancerous lesions. It is a pathologic marker and probably an underlying cause of oxidative damage and inflammation at tumor initiation. Inhibition of the aberrant promoter methylation could therefore be an effective mean to prevent carcinogenesis. Several isothiocyanates, including phenethyl isothiocyanate (PEITC), found naturally in cruciferous vegetables, induced growth arrest and apoptosis in prostate cancer cells in culture and xenografts. The effects of PEITC to reactivate GSTP1 were investigated. Exposure of prostate cancer LNCaP cells to PEITC inhibited the activity and level of histone deacetylases (HDACs), and induced selective histone acetylation and methylation for chromatin unfolding. Concurrently PEITC demethylated the promoter and restored the unmethylated GSTP1 in both androgen-dependent and -independent LNCaP cancer cells to the level found in normal prostatic cells, as quantified by methylation-specific PCR and pyrosequencing. The dual action of PEITC on both the DNA and chromatin was more effective than 5'-Aza-2'-deoxycytidine, sodium butyrate, or trichostatin A (TSA), and may de-repress the methyl-binding domain (MBD) on gene transcription. The PEITC-mediated cross-talk between the DNA and chromatin in demethylating and reactivating GSTP1 genes, which is critically inactivated in prostate carcinogenesis, underlines a primary mechanism of cancer chemoprevention."

[5] Hypoxia.

When a tumor outgrows its blood supply, affected cells respond by inducing hypoxia inducible factor (HIF-1α), which makes them extremely difficult to kill. A key downstream event is the production of vascular endothelial growth factor (VEGF), which is needed for the generation of new blood vessels. Cancer cells do not want to be hypoxic. Ignore sites that claim that "Cancer hates oxygen."

[5a] (2013 - U.S.)

"Phenethyl isothiocyanate (PEITC), a natural dietary isothiocyanate, inhibits angiogenesis but the molecular mechanisms that underlie this effect are not known. In this study, under hypoxic conditions (1% O2), we examined the effect of PEITC on the intracellular level of the hypoxia inducible factor (HIF-1α) and extracellular level of the vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that PEITC suppressed the HIF-1α accumulation during hypoxia in human glioma U87, human prostate cancer DU145, colon cancer HCT116, liver cancer HepG2, and breast cancer SkBr3 cells."

[6] Androgen Receptor [AR]

[6a] (2013 - U.S. & China)

"Androgen receptor (AR) signaling is critical for all aspects of prostate growth and tumorigenesis. The glucosinolate-derived phenethyl isothiocyanate (PEITC) has recently been demonstrated to reduce the risk of prostate cancer (PCa) and inhibit PCa cell growth. We previously reported that p300/CBP-associated factor (PCAF), a co-regulator for AR, is upregulated in PCa cells through suppression of the mir-17 gene."

"Our results indicate that PEITC inhibits AR-regulated transcriptional activity and cell growth of PCa cells through miR-17-mediated suppression of PCAF ..."

[6b] (2006 - U.S.)

"PEITC represses AR transcription and expression, and mediates growth arrest in androgen dependent and independent prostate cancer cells. With the AR modulation and growth attenuation, PEITC and possibly other isothiocyanates, may prevent and inhibit hormone sensitive and refractory prostate cancer."

[7] Cell death (apoptosis or autophagy) & cell cycle arrest.

[7a] (2011 - Taiwan)

"Phenethyl isothiocyanate (PEITC), one of many compounds found in cruciferous vegetables, has been reported as a potential anticancer agent. In earlier studies, PEITC was shown to inhibit cell growth and induction of apoptosis in many cancer cell lines. However, no report has shown whether PEITC can induce apoptosis in human prostate cancer cells. Herein, we aimed to determine whether PEITC has anticancer activity in DU 145 human prostate cancer cells. As a result, we found that PEITC induced a dose-dependent decrease in cell viability through induction of cell apoptosis and cell cycle arrest in the G(2)/M phase of DU 145 cells."

[7b] (2011 - U.S.)

"In this transgenic model, dietary PEITC suppressed prostate cancer progression by induction of autophagic cell death. Potential biomarkers to assess the response to PEITC treatment in plasma were identified."

[7c] (2009 - U.S.)

"We now show, for the first time, that PEITC treatment triggers Atg5-dependent autophagic and apoptotic cell death in human prostate cancer cells."

[7d] (2008 - U.S.)

"PEITC-induced G2-M cell phase arrest and inhibited the expression of alpha- and beta-tubulin proteins in a number of human prostatic carcinoma cell lines."

[7e] (2008 - U.S.)

"... this study shows for the first time that PEITC can arrest HT-29 cells in G1 phase by down-regulation of cyclins through the activation of p38 MAPK signaling pathway."

[7f] (2005 - U.S.)

"... results indicate that involvement of MAPKs in apoptosis induction by PEITC in human prostate cancer cells is cell line-specific."

[7g] (2005 - U.S.)

"The results of the present study indicate that caspase-dependent apoptosis by PEITC is mediated by Bak and Bax proteins."

[7h] (2004 - U.S.)

"... our data indicate that PEITC-induced cell cycle arrest in PC-3 cells is likely due to proteasome-mediated degradation of Cdc25C and Cdk1, and ectopic expression of Bcl-2 fails to confer resistance to PEITC-induced apoptosis. Furthermore, the results of the present study point toward involvement of both caspase-8- and caspase-9-mediated pathways in apoptosis induction by PEITC."

[7i] (2002 - U.S.)

"... the results of the present study indicate that p53 is not essential for PEITC-induced apoptosis and that the PEITC-induced apoptosis in PC-3 human prostate carcinoma cell line is mediated by ERKs. Thus, it seems reasonable to postulate that PEITC may be effective against tumors with normal as well as mutant p53."

[8] Reactive oxygen species [ROS]-mediated death.

Typically, people use natural antioxidants to protect normal cells. With cancer, the common approach is to induce reactive oxygen species [ROS]. For natural antioxidants, this involves doses at which they become pro-oxidant.

[8a] (2010 - U.S.)

"... the present study provides novel insight into the molecular circuitry of PEITC-induced cell death involving ROS production due to inhibition of complex III and OXPHOS."

[8b] (2006 - U.S.)

"... the present study indicates that the PEITC-induced apoptosis in PC-3 cells is mediated by ROS-dependent disruption of the mitochondrial membrane potential and regulated by Bax and Bid."

[9] PEITC + Docetaxel.

[9a] (2010 - U.S.)

"Pharmacologic concentrations of PEITC augmented Docetaxel-induced apoptosis in PC-3 and DU145 cells in association with suppression of Bcl-2 and XIAP protein levels and induction of Bax and Bak. The PEITC-Docetaxel combination was markedly more efficacious against PC-3 xenograft in vivo compared with PEITC or Docetaxel alone. Significantly higher counts of apoptotic bodies were also observed in tumor sections from mice treated with the PEITC-Docetaxel combination compared with PEITC or Docetaxel alone."

[X] Other studies.

[Xa] "CXCR4 is a novel target of cancer chemopreventative isothiocyanates in prostate cancer cells."

[Xb] "In vitro and in vivo effects of phenethyl isothiocyanate treatment on vimentin protein expression in cancer cells."

[Xc] "miR-141 modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein."

[Xd] "Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate."

[Xe] "Inhibition of androgen-responsive LNCaP prostate cancer cell tumor xenograft growth by dietary phenethyl isothiocyanate correlates with decreased angiogenesis and inhibition of cell attachment."

[Xf] "Phenethyl isothiocyanate suppresses inhibitor of apoptosis family protein expression in prostate cancer cells in culture and in vivo."

[Xg] "Notch activation by phenethyl isothiocyanate attenuates its inhibitory effect on prostate cancer cell migration."

[Xh] "Differential response of normal (PrEC) and cancerous human prostate cells (PC-3) to phenethyl isothiocyanate-mediated changes in expression of antioxidant defense genes."

[Xi] "p66Shc is indispensable for phenethyl isothiocyanate-induced apoptosis in human prostate cancer cells."

[Xj] "Targeting protein kinase C (PKC) and telomerase by phenethyl isothiocyanate (PEITC) sensitizes PC-3 cells towards chemotherapeutic drug-induced apoptosis."

[Xk] "Phenethyl isothiocyanate inhibits STAT3 activation in prostate cancer cells."

[Xl] "Phenethyl isothiocyanate, a cancer chemopreventive constituent of cruciferous vegetables, inhibits cap-dependent translation by regulating the level and phosphorylation of 4E-BP1."

[Xm] "Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo."

[Xn] "Phenylethyl isothiocyanate induces apoptotic signaling via suppressing phosphatase activity against c-Jun N-terminal kinase."

-Patrick

[1] en.wikipedia.org/wiki/Phene...

[2] swansonvitamins.com/swanson...

[3] ncbi.nlm.nih.gov/pubmed/282...

[4a] ncbi.nlm.nih.gov/pubmed/278...

[4b] ncbi.nlm.nih.gov/pubmed/268...

[4c] ncbi.nlm.nih.gov/pubmed/246...

[4d] ncbi.nlm.nih.gov/pubmed/206...

[4e] ncbi.nlm.nih.gov/pubmed/186...

[4f] ncbi.nlm.nih.gov/pubmed/169...