Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells

Martin Albrecht, Wenguo Jiang, James Kumi-Diaka, Ephraim P. Lansky, Lyndon M. Gommersall, Amit Patel, Robert E. Mansel, Ishak Neeman, Albert A. Geldof, Moray J. Campbell

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO2-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED50) was 70 μg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED50 = 250 μg/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G2/M cells (P < .05) by treatment with Oil (35 μg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 μg/mL) resulted in significant 2.3 ± 0.001-fold (mean ± SEM) up-regulation of the cyclin-dependent kinase inhibitor p21(waf1/cip1) (P < .01) and 0.6 ± 0.14-fold down-regulation of c-myc (P < .05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.

Original languageEnglish
Pages (from-to)274-283
Number of pages10
JournalJournal of Medicinal Food
Volume7
Issue number3
DOIs
Publication statusPublished - 1 Sep 2004

Cite this

Albrecht, M., Jiang, W., Kumi-Diaka, J., Lansky, E. P., Gommersall, L. M., Patel, A., ... Campbell, M. J. (2004). Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. Journal of Medicinal Food, 7(3), 274-283. https://doi.org/10.1089/jmf.2004.7.274
Albrecht, Martin ; Jiang, Wenguo ; Kumi-Diaka, James ; Lansky, Ephraim P. ; Gommersall, Lyndon M. ; Patel, Amit ; Mansel, Robert E. ; Neeman, Ishak ; Geldof, Albert A. ; Campbell, Moray J. / Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. In: Journal of Medicinal Food. 2004 ; Vol. 7, No. 3. pp. 274-283.
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title = "Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells",
abstract = "We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO2-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50{\%} (ED50) was 70 μg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED50 = 250 μg/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11{\%} to 22{\%} in G2/M cells (P < .05) by treatment with Oil (35 μg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 μg/mL) resulted in significant 2.3 ± 0.001-fold (mean ± SEM) up-regulation of the cyclin-dependent kinase inhibitor p21(waf1/cip1) (P < .01) and 0.6 ± 0.14-fold down-regulation of c-myc (P < .05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.",
keywords = "Apoptosis, Chemoprevention, Flavonoid, P2 1, Phytoestrogen, Prostate cancer, Punicic acid",
author = "Martin Albrecht and Wenguo Jiang and James Kumi-Diaka and Lansky, {Ephraim P.} and Gommersall, {Lyndon M.} and Amit Patel and Mansel, {Robert E.} and Ishak Neeman and Geldof, {Albert A.} and Campbell, {Moray J.}",
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Albrecht, M, Jiang, W, Kumi-Diaka, J, Lansky, EP, Gommersall, LM, Patel, A, Mansel, RE, Neeman, I, Geldof, AA & Campbell, MJ 2004, 'Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells' Journal of Medicinal Food, vol. 7, no. 3, pp. 274-283. https://doi.org/10.1089/jmf.2004.7.274

Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. / Albrecht, Martin; Jiang, Wenguo; Kumi-Diaka, James; Lansky, Ephraim P.; Gommersall, Lyndon M.; Patel, Amit; Mansel, Robert E.; Neeman, Ishak; Geldof, Albert A.; Campbell, Moray J.

In: Journal of Medicinal Food, Vol. 7, No. 3, 01.09.2004, p. 274-283.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells

AU - Albrecht, Martin

AU - Jiang, Wenguo

AU - Kumi-Diaka, James

AU - Lansky, Ephraim P.

AU - Gommersall, Lyndon M.

AU - Patel, Amit

AU - Mansel, Robert E.

AU - Neeman, Ishak

AU - Geldof, Albert A.

AU - Campbell, Moray J.

PY - 2004/9/1

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N2 - We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO2-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED50) was 70 μg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED50 = 250 μg/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G2/M cells (P < .05) by treatment with Oil (35 μg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 μg/mL) resulted in significant 2.3 ± 0.001-fold (mean ± SEM) up-regulation of the cyclin-dependent kinase inhibitor p21(waf1/cip1) (P < .01) and 0.6 ± 0.14-fold down-regulation of c-myc (P < .05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.

AB - We completed a multicenter study of the effects of pomegranate cold-pressed (Oil) or supercritical CO2-extracted (S) seed oil, fermented juice polyphenols (W), and pericarp polyphenols (P) on human prostate cancer cell xenograft growth in vivo, and/or proliferation, cell cycle distribution, apoptosis, gene expression, and invasion across Matrigel, in vitro. Oil, W, and P each acutely inhibited in vitro proliferation of LNCaP, PC-3, and DU 145 human cancer cell lines. The dose of P required to inhibit cell proliferation of the prostate cancer cell line LNCaP by 50% (ED50) was 70 μg/mL, whereas normal prostate epithelial cells (hPrEC) were significantly less affected (ED50 = 250 μg/mL). These effects were mediated by changes in both cell cycle distribution and induction of apoptosis. For example, the androgen-independent cell line DU 145 showed a significant increase from 11% to 22% in G2/M cells (P < .05) by treatment with Oil (35 μg/mL) with a modest induction of apoptosis. In other cell lines/treatments, the apoptotic response predominated, for example, in PC-3 cells treated with P, at least partially through a caspase 3-mediated pathway. These cellular effects coincided with rapid changes in mRNA levels of gene targets. Thus, 4-hour treatment of DU 145 cells with Oil (35 μg/mL) resulted in significant 2.3 ± 0.001-fold (mean ± SEM) up-regulation of the cyclin-dependent kinase inhibitor p21(waf1/cip1) (P < .01) and 0.6 ± 0.14-fold down-regulation of c-myc (P < .05). In parallel, all agents potently suppressed PC-3 invasion through Matrigel, and furthermore P and S demonstrated potent inhibition of PC-3 xenograft growth in athymic mice. Overall, this study demonstrates significant antitumor activity of pomegranate-derived materials against human prostate cancer.

KW - Apoptosis

KW - Chemoprevention

KW - Flavonoid

KW - P2 1

KW - Phytoestrogen

KW - Prostate cancer

KW - Punicic acid

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U2 - 10.1089/jmf.2004.7.274

DO - 10.1089/jmf.2004.7.274

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JO - Journal of Medicinal Food

JF - Journal of Medicinal Food

SN - 1096-620X

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