Effective prostate cancer chemopreventive intervention with green tea polyphenols in the TRAMP model depends on Thestage of the disease

Vaqar Mustafa Adhami, Imtiaz Ahmad Siddiqui, Sami Sarfaraz, Sabih Islam Khwaja, Bilal Hafeez, Nihal Ahmad, Hasan Mukhtar

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Purpose: We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP. Experimental Design: GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF) -I/IGF binding protein-3 and IGF signaling. Results: Tumor-free survival was extended to 38 weeks (P < 0.001) in group 1, 31 weeks (P < 0.01) in group 2, and 24 weeks (P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common. Conclusions: Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.

Original languageEnglish (US)
Pages (from-to)1947-1953
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number6
DOIs
StatePublished - Mar 15 2009

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Polyphenols
Tea
Prostate
Prostatic Neoplasms
Adenocarcinoma
Prostatic Intraepithelial Neoplasia
Insulin-Like Growth Factor I
Transgenic Mice
Phosphatidylinositol 3-Kinase
Insulin-Like Growth Factor Binding Protein 3
Extracellular Signal-Regulated MAP Kinases
Chemoprevention
Somatomedins
Life Expectancy
Drinking Water
Research Design
Magnetic Resonance Imaging
Weights and Measures
Survival
Water

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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Effective prostate cancer chemopreventive intervention with green tea polyphenols in the TRAMP model depends on Thestage of the disease. / Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Sarfaraz, Sami; Khwaja, Sabih Islam; Hafeez, Bilal; Ahmad, Nihal; Mukhtar, Hasan.

In: Clinical Cancer Research, Vol. 15, No. 6, 15.03.2009, p. 1947-1953.

Research output: Contribution to journalArticle

Adhami, Vaqar Mustafa ; Siddiqui, Imtiaz Ahmad ; Sarfaraz, Sami ; Khwaja, Sabih Islam ; Hafeez, Bilal ; Ahmad, Nihal ; Mukhtar, Hasan. / Effective prostate cancer chemopreventive intervention with green tea polyphenols in the TRAMP model depends on Thestage of the disease. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 6. pp. 1947-1953.
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abstract = "Purpose: We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP. Experimental Design: GTP infusion (0.1{\%} in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF) -I/IGF binding protein-3 and IGF signaling. Results: Tumor-free survival was extended to 38 weeks (P < 0.001) in group 1, 31 weeks (P < 0.01) in group 2, and 24 weeks (P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common. Conclusions: Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.",
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AU - Khwaja, Sabih Islam

AU - Hafeez, Bilal

AU - Ahmad, Nihal

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AB - Purpose: We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP. Experimental Design: GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: (a) 6 weeks (group 1, normal prostate), (b) 12 weeks (group 2, prostatic intraepithelial neoplasia), (c) 18 weeks (group 3, well-differentiated adenocarcinoma), and (b) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF) -I/IGF binding protein-3 and IGF signaling. Results: Tumor-free survival was extended to 38 weeks (P < 0.001) in group 1, 31 weeks (P < 0.01) in group 2, and 24 weeks (P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common. Conclusions: Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.

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