Safety and Chemopreventive Effect of Polyphenon E in Preventing Early and Metastatic Progression of Prostate Cancer in TRAMP Mice

Kim, Seung Joon; Amankwah, Ernest K.; Connors, Shahnjayla K.; Park, Hyun Y.; Rincon, Maria; Cornnell, Heather H.; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya Yu; Engelman, Robert W.; Kumar, Nagi B.; Park, Jong Y.

doi:10.1158/1940-6207.capr-13-0427-t

Cited by 25 publications

(25 citation statements)

References 65 publications

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“…Preclinical studies of GTCs (20–23) have shown significant reductions in tumor size and multiplicity in the PCa TRAMP mouse model, as well as potent and selective pro-apoptotic activity in PCa cell lines (16, 18–23). Phase I/II studies (24–30) have demonstrated good bioavailability and tolerability at doses ranging from 200–1200 mg EGCG per day. Bettuzzi et al reported a significant reduction in prostate cancer in men with HGPIN randomized to receive one-year of EGCG (24, 25).…”

Section: Introductionmentioning

confidence: 99%

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

Kumar

Pow‐Sang

Egan

et al. 2015

Cancer Prevention Research

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108

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Preclinical, epidemiological and prior clinical trial data suggest that green tea catechins (GTCs) may reduce prostate cancer (PCa) risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E® (PolyE), a proprietary mixture of GTCs, containing 400 mg (–)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year PCa rates on the two study arms. No differences in the number of PCa cases were observed: 5/49 (PolyE) versus 9/48 (placebo), P=0.25. A secondary endpoint comparing the cumulative rate of PCa plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3/26 (PolyE) versus 10/25 (placebo), P<0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared to the placebo arm (5/25). A decrease in serum prostate specific antigen (PSA) was observed on the PolyE arm [−0.87 ng/ml (95%CI: −1.66, −0.09)]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of PCa in men with baseline HGPIN or ASAP.

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Section: Introductionmentioning

confidence: 99%

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

Kumar

Pow‐Sang

Egan

et al. 2015

Cancer Prevention Research

Self Cite

108

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“…One of the studies showed that EPG containing green tea extract significantly reduced circulating tumor cells in breast cancer patients (Samavat et al, 2016). Kim et al (2014) showed that EPG inhibits progression of prostate cancer and metastasis in TRAMP mice (Kim et al, 2014). Another natural compound that affects DNA methylation is curcumin (Liu et al, 2009).…”

Section: Targeting Dna Modifications In Cancer Therapymentioning

confidence: 99%

Key actors in cancer therapy: epigenetic modifiers

Akar¹,

Selvi²,

Ulukaya³

et al. 2019

Turk J Biol

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Epigenetic reprogramming plays a crucial role in the tumorigenicity and maintenance of tumor-specific gene expression that especially occurs through DNA methylation and/or histone modifications. It has well-defined mechanisms. It is known that alterations in the DNA methylation pattern and/or the loss of specific histone acetylation/methylation markers are related to several hallmarks of cancer, such as drug resistance, stemness, epithelial-mesenchymal transition, and metastasis. It has also recently been highlighted that epigenetic alterations are critical for the regulation of the stemlike properties of cancer cells (tumor-initiating cells; cancer stem cells). Cancer stem cells are thought to be responsible for the recurrence of cancer which makes the patient return to the clinic with metastatic tumor tissue. Hence, the dysregulation of epigenetic machinery represents potential new therapeutic targets. Therefore, compounds with epigenetic activities have become crucial for developing new therapy regimens (e.g., antimetastatic agents) in the fight against cancer. Here, we review the epigenetic modifiers that have already been used in the clinic and/or in clinical trials, related preclinical studies in cancer therapy, and the smart combination strategies that target cancer stem cells along with the other cancer cells. The emerging role of epitranscriptome (RNA epigenetic) in cancer therapy has also been included in this review as a new avenue and potential target for the better management of cancer-beneficial epigenetic machinery.

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“…Adverse effects were observed in Swiss Webster mice at 2000 mg/kg/day [276], approximately 200 fold higher than the toxic dose in humans; 1000 mg/kg/day Polyphenon E were well tolerated by C57Bl/6J mice [277]. Similarly, goitrogenic effects were observed in rats only in food concentrations in excess of 0.625%, equivalent to 600 mg/kg/day [278].…”

Section: Risk-benefit Analysismentioning

confidence: 99%

Green Tea and Its Extracts in Cancer Prevention and Treatment

et al. 2017

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Green tea (GT) and green tea extracts (GTE) have been postulated to decrease cancer incidence. In vitro results indicate a possible effect; however, epidemiological data do not support cancer chemoprevention. We have performed a PubMED literature search for green tea consumption and the correlation to the common tumor types lung, colorectal, breast, prostate, esophageal and gastric cancer, with cohorts from both Western and Asian countries. We additionally included selected mechanistical studies for a possible mode of action. The comparability between studies was limited due to major differences in study outlines; a meta analysis was thus not possible and studies were evaluated individually. Only for breast cancer could a possible small protective effect be seen in Asian and Western cohorts, whereas for esophagus and stomach cancer, green tea increased the cancer incidence, possibly due to heat stress. No effect was found for colonic/colorectal and prostatic cancer in any country, for lung cancer Chinese studies found a protective effect, but not studies from outside China. Epidemiological studies thus do not support a cancer protective effect. GT as an indicator of as yet undefined parameters in lifestyle, environment and/or ethnicity may explain some of the observed differences between China and other countries.

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Safety and Chemopreventive Effect of Polyphenon E in Preventing Early and Metastatic Progression of Prostate Cancer in TRAMP Mice

Cited by 25 publications

References 65 publications

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention

Key actors in cancer therapy: epigenetic modifiers

Green Tea and Its Extracts in Cancer Prevention and Treatment

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