This post is prompted by a new study [20].
But first a review of PCa literature.
{{{For those who want the bottom line: "Our results indicate that administration of DBM and PEITC in combination may be an effective strategy for inhibiting/delaying the progression of prostate cancer to androgen independence."}}}
Interest in licorice use against PCa was spurred by its inclusion in the PC-SPES formula (chrysanthemum, isatis, licorice, Ganoderma lucidum, Panax pseudo-ginseng, Rabdosia rubescens, saw palmetto, and scutellaria).
Regardless of one's view of the PC-SPES scandal, Dr Sophie Chen (New York Medical College) had sound reasons for the listed ingredients.
It turns out that a number of licorice components demonstrate anti-PCa activity.
[1] (2000) - U.S.
"We recently demonstrated that the herbal combination PC-SPES, which contains licorice root, had potent estrogenic activity in vitro, in animals, and in patients with prostate cancer. Licochalcone-A (LA) is one flavonoid extracted from licorice root with antiparasitic and anti-tumor activity, but the effect on the human estrogen receptor and mechanism of anti-tumor activity is unknown. Recent studies demonstrated that the mechanism of cytotoxic effect by some estrogens may involve modulation of the anti-apoptotic protein bcl-2."
Our "data demonstrate that LA is a phytoestrogen with anti-tumor activity and is capable of modulating bcl-2 protein expression. The modulation of bcl-2 may be dependent on specific structural differences between LA and the parent compound chalcone and independent of LA estrogenicity."
[2] (2002) - same team as [1].
"We recently demonstrated that the herbal combination PC-SPES, which contains licorice root, had anti-prostate cancer activity attributable to estrogen(s) that produced a chemical castration. A recent study also demonstrated that licorice root alone decreased circulating testosterone in men. Other studies demonstrated antitumor activity of PC-SPES in vitro associated with decreased expression of the anti-apoptotic protein Bcl-2 and in patients independent of chemical castration, suggesting that other mechanisms of antitumor activity exist separate from chemical castration. In the present study, we assessed licorice root extract for effects on Bcl-2 to identify novel cytotoxic derivatives."
Our "data demonstrate that licorice root contains beta-hydroxy-DHP, which induced Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest, in breast and prostate tumor cells, similarly to the action of more complex (MW >800) antimicrotubule agents used clinically."
[3] (2002) - U.S.
"Dibenzoylmethane (DBM), a minor beta-diketone constituent of licorice and sunscreens, has been shown to exhibit anti-neoplastic effects in chemically induced skin and mammary cancers in several animal models. To date, no mechanism for the growth inhibitory effects of DBM on prostate cancer cells has been proposed. In this study, we examined the effects of DBM on the growth and cell cycle kinetics of several human prostate carcinoma cell lines. "
"... analyses showed deregulation of the cell cycle, which correlated with the observed cytostatic effects of DBM in prostate carcinoma cells."
[4] (2003) - Japan
"Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. In this study, we investigated the anti-tumor effect of isoliquiritigenin on prostate cancer in vitro."
"Isoliquiritigenin significantly inhibited the proliferation of prostate cancer cell lines in a dose-dependent and time-dependent manner."
[5] (2004) - U.S.
"Licochalcone (LA) is a novel estrogenic flavonoid isolated from PC-SPES composition herb licorice root that was reported to show significant antitumor activity in various malignant human cell lines. To better understand its anti-CaP activities, we have investigated LA-elicited growth control and induction of apoptosis using androgen-independent p53-null PC-3 prostate cancer cells. LA induced modest level of apoptosis but had more pronounced effect on cell cycle progression arresting cells in G2/M, accompanied by suppression of cyclin B1 and cdc2."
[6] (2006) - S. Korea.
"Isoliquiritigenin (ISL), a simple chalcone derivative, 4,2',4'-trihydroxychalcone, found in licorice, shallot and bean sprouts, has been reported to have chemoprotective effects. To examine the effects of ISL on the growth of prostate cancer cells, we cultured MAT-LyLu (MLL) rat and DU145 human prostate cancer cells with various concentrations (0-20 micromol/L) of ISL. Treatment of the cells with increasing concentrations of ISL led to dose-dependent decreases in the viable cell numbers in both DU145 and MLL cells".
Our "results indicate that ISL inhibits prostate cancer cell growth by the induction of apoptosis, which is mediated through mitochondrial events, which are associated with an evident disruption of the mitochondrial membrane potential, and the release of cytochrome c and Smac/Diablo, and the activation of caspase-9."
[7] (2006) - same team as [6].
"Overexpression of members of the ErbB receptor family is a frequently observed event in several human cancers, and ErbB receptors currently constitute the primary targets of anticancer strategies."
Our "results indicate that ISL inhibits the proliferation of prostate cancer cells, at least in part, via the inhibition of ErbB3 signaling and the PI3K/Akt pathway."
[8] (2008) - U.K.
"Glycyrrhetinic acid (GA) is the active metabolite of glycyrrhizic acid, one of the components of liquorice extract. It has been shown to possess anti-inflammatory activity and to inhibit hepatic tumour growth. In this preliminary study, we have shown that GA could significantly reduce the rate of proliferation of LNCaP androgen dependent prostate cancer cells, whereas it had no effect on proliferation of PC3 and DU145 androgen-independent prostate cancer cells."
[9] (2008) - same team as [6].
Our "results provide evidence for the role of ISL as a potent antimetastatic agent, which can markedly inhibit the metastatic and invasive capacity of prostate cancer cells. The inhibition of JNK/AP-1 signaling may be one of the mechanisms by which ISL inhibits cancer cell invasion and migration."
[10] (2008) - U.S.
"Glycyrrhizin, a triterpene compound isolated from roots of licorice has been found to exhibit potent in vitro cytotoxic activity against several human cancer cell lines. In this study, we evaluated the effects of glycyrrhizin on the viability of two human prostate cancer cells LNCaP (hormone-dependent) and DU-145 (hormone-independent) in vitro. Cell viability assay showed that glycyrrhizin inhibited the cell proliferation of prostate cancer cells in a time- and dose-dependent manner. The decreased viability of prostate cancer cells was due to apoptosis as confirmed by Annexin-V FITC flow cytometric analyses. Glycyrrhizin also caused DNA damage in DU-145 and LNCaP cells in a time-dependent manner."
[11] (2009) - same team as [6].
"We demonstrate that ISL promotes cell cycle arrest in DU145 and MLL cells, thereby providing insights into the mechanisms underlying its antitumorigenic activities."
[12] (2009) - U.S.
"Dibenzoylmethane (DBM), a minor beta-diketone constituent of licorice, has been shown to exhibit antineoplastic effects in prostate cancer cell lines by induction of cell cycle arrest and regulation of androgen receptor expression."
"Our findings suggest that DBM blocks the growth and progression of prostate cancer in TRAMP mice via modulation of tumor cell cycle regulation and therefore merits its consideration for future clinical intervention of human prostate cancer."
[13] (2009) - Taiwan.
"Licorice is a common Chinese medicinal herb with antitumor activity. Some components in licorice root have been shown to induce cell cycle arrest or apoptosis in cancer cells. This paper demonstrates for the first time that licorice Glycyrrhiza glabra and its component licochalcone-A (LA) can induce autophagy in addition to apoptosis in human LNCaP prostate cancer cells. Exposure of cells to licorice or LA resulted in several confirmed characteristics of autophagy ..."
"Autophagy induction was accompanied by down-regulation of Bcl-2 and inhibition of the mammalian target of rapamycin (mTOR) pathway. In summary, licorice can induce caspase-dependent and autophagy-related cell death in LNCaP cells."
[14] (2010) - same team as [6].
"Glycyrrhiza uralensis (licorice) is one of the most frequently prescribed ingredients in Oriental medicine, and licorice extract has been shown to exert anti-carcinogenic effects. However, its use as a cancer chemopreventive agent is rather limited, due to the fact that its principal component, glycyrrhizin, is known to induce hypertension."
"This study determined the effects of a hexane/ethanol extract of G. uralensis (HEGU), which contains undetectable amounts of glycyrrhizin, on the apoptosis of androgen-insensitive DU145 cells. HEGU induced apoptosis ..."
[15] (2010) - China.
"The results of the present study suggest that ISL, a natural anti-oxidant, selectively inhibits the proliferation of prostate cancer C4-2 cells, which may be attributed, in part, to defective AMPK and ERK signalling pathways in C4-2 compared with IEC-6 cells."
[16] (2010) - same team as [6].
"Hexane-ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells."
[17] (2011) - same team as [6].
"Hexane/ethanol extract of Glycyrrhiza uralensis and its active compound isoangustone A induce G1 cycle arrest in DU145 human prostate" cells.
[18] (2013) - Korea.
"CDK2 and mTOR are direct molecular targets of isoangustone A in the suppression of human prostate cancer cell growth."
[19] (2018) - China.
"Antineoplastic activity of isoliquiritigenin, a chalcone compound, in androgen-independent human prostate cancer cells linked to G2/M cell cycle arrest and cell apoptosis."
[20] (2018) - China / U.S.
The new study used PEITC which is present at high levels in watercress, & dibenzoylmethane.
"Phenethyl isothiocyanate in combination with dibenzoylmethane inhibits the androgen-independent growth of prostate cancer cells."
"PEITC and DBM in combination had stronger effects on inhibiting the growth and inducing apoptosis than either compound alone in cultured prostate cancer cells. The combination also strongly inhibited cell migration and the formation of tumorspheres in VCaP cells. Mechanistic studies showed that the combined effects of PEITC and DBM on growth inhibition and apoptosis were associated with suppression of nuclear factor-κB (NF-κB), and a decrease in the levels of survivin and phospho-Akt (pAkt)."
"In the in vivo study, SCID mice bearing VCaP tumors were surgically castrated and treated with PEITC and/or DBM. Treatment with PEITC and DBM in combination resulted in a strong inhibition of the progression of androgen-dependent VCaP prostate tumors to androgen independence."
"Our results indicate that administration of DBM and PEITC in combination may be an effective strategy for inhibiting/delaying the progression of prostate cancer to androgen independence."
...
A strange British treat back in the day was chewing on licorice root, which could be had for a penny or less. I wouldn't do that today, though.
DGL is a licorice supplement that contains very little glycyrrhizinic acid:
swansonvitamins.com/swanson...
It does not have the toxicity of licorice root.
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/109...
[2] ncbi.nlm.nih.gov/pubmed/118...
[3] ncbi.nlm.nih.gov/pubmed/118...
[4] ncbi.nlm.nih.gov/pubmed/127...
[5] ncbi.nlm.nih.gov/pubmed/153...
[6] ncbi.nlm.nih.gov/pubmed/165...
[7] ncbi.nlm.nih.gov/pubmed/174...
[8] ncbi.nlm.nih.gov/pubmed/184...
[9] ncbi.nlm.nih.gov/pubmed/188...
[10] ncbi.nlm.nih.gov/pubmed/190...
[11] ncbi.nlm.nih.gov/pubmed/192...
[12] ncbi.nlm.nih.gov/pubmed/197...
[13] ncbi.nlm.nih.gov/pubmed/197...
[14] ncbi.nlm.nih.gov/pubmed/202...
[15] ncbi.nlm.nih.gov/pubmed/204...
[16] ncbi.nlm.nih.gov/pubmed/204...
[17] ncbi.nlm.nih.gov/pubmed/214...
[18] ncbi.nlm.nih.gov/pubmed/237...
[19] ncbi.nlm.nih.gov/pubmed/292...
[20] ncbi.nlm.nih.gov/pubmed/295...
Food Funct. 2018 Mar 29. doi: 10.1039/c7fo01983a. [Epub ahead of print]
Phenethyl isothiocyanate in combination with dibenzoylmethane inhibits the androgen-independent growth of prostate cancer cells.
Huang H1, He Y1, Zhang L1, Xiang H1, Li D2, Liu W2, Xu XT2, Goodin S3, Zhang K2, Zheng X4.
Author information
1
Allan H. Conney Laboratory for Anticancer Research, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, P. R. China. hrhuang@gdut.edu.cn.
2
International Healthcare Innovation Institute (Jiangmen), Jiangmen city, Guangdong Province 529020, China and School of Chemical Engineering and Environment, Wuyi University, Jiangmen city, 529020, China.
3
The Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
4
Allan H. Conney Laboratory for Anticancer Research, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, P. R. China. hrhuang@gdut.edu.cn and Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA. xizheng@pharmacy.rutgers.edu.
Abstract
Phenethyl isothiocyanate (PEITC) is a naturally occurring compound found in some cruciferous vegetables. Dibenzoylmethane (DBM) is a minor constituent of licorice. Both compounds have been shown to exert anticancer activities. In the present study, we determined the effects of PEITC and DBM alone or in combination on androgen-independent growth of human prostate cancer cells cultured in vitro and prostate VCaP xenograft tumors in severe combined immunodeficient (SCID) mice. PEITC and DBM in combination had stronger effects on inhibiting the growth and inducing apoptosis than either compound alone in cultured prostate cancer cells. The combination also strongly inhibited cell migration and the formation of tumorspheres in VCaP cells. Mechanistic studies showed that the combined effects of PEITC and DBM on growth inhibition and apoptosis were associated with suppression of nuclear factor-κB (NF-κB), and a decrease in the levels of survivin and phospho-Akt (pAkt). In the in vivo study, SCID mice bearing VCaP tumors were surgically castrated and treated with PEITC and/or DBM. Treatment with PEITC and DBM in combination resulted in a strong inhibition of the progression of androgen-dependent VCaP prostate tumors to androgen independence. Our results indicate that administration of DBM and PEITC in combination may be an effective strategy for inhibiting/delaying the progression of prostate cancer to androgen independence.
PMID: 29595853 DOI: 10.1039/c7fo01983a
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