Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice

Xi Zheng, Richard L. Chang, Xiao Xing Cui, Gina E. Avila, Vidya Hebbar, Mark Garzotto, Weichung Joe Shih, Yong Lin, Shou En Lu, Arnold B. Rabson, Ah Ng Tony Kong, Allan H. Conney

Research output: Contribution to journalArticle

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Abstract

Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice. Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2). Results: Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33% in experiment 1 and 100% in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17% and 57% of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression. Conclusions: TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted.

Original languageEnglish (US)
Pages (from-to)3444-3451
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number11 I
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

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Tetradecanoylphorbol Acetate
Paclitaxel
Heterografts
Cultured Cells
Prostatic Neoplasms
Neoplasms
Growth
Cell Culture Techniques
In Vitro Techniques
Therapeutics
Research Design
Phosphotransferases
Clinical Trials
Apoptosis
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice. / Zheng, Xi; Chang, Richard L.; Cui, Xiao Xing; Avila, Gina E.; Hebbar, Vidya; Garzotto, Mark; Shih, Weichung Joe; Lin, Yong; Lu, Shou En; Rabson, Arnold B.; Kong, Ah Ng Tony; Conney, Allan H.

In: Clinical Cancer Research, Vol. 12, No. 11 I, 01.06.2006, p. 3444-3451.

Research output: Contribution to journalArticle

Zheng, Xi ; Chang, Richard L. ; Cui, Xiao Xing ; Avila, Gina E. ; Hebbar, Vidya ; Garzotto, Mark ; Shih, Weichung Joe ; Lin, Yong ; Lu, Shou En ; Rabson, Arnold B. ; Kong, Ah Ng Tony ; Conney, Allan H. / Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 11 I. pp. 3444-3451.
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title = "Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice",
abstract = "Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice. Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2). Results: Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33{\%} in experiment 1 and 100{\%} in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17{\%} and 57{\%} of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression. Conclusions: TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted.",
author = "Xi Zheng and Chang, {Richard L.} and Cui, {Xiao Xing} and Avila, {Gina E.} and Vidya Hebbar and Mark Garzotto and Shih, {Weichung Joe} and Yong Lin and Lu, {Shou En} and Rabson, {Arnold B.} and Kong, {Ah Ng Tony} and Conney, {Allan H.}",
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T1 - Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice

AU - Zheng, Xi

AU - Chang, Richard L.

AU - Cui, Xiao Xing

AU - Avila, Gina E.

AU - Hebbar, Vidya

AU - Garzotto, Mark

AU - Shih, Weichung Joe

AU - Lin, Yong

AU - Lu, Shou En

AU - Rabson, Arnold B.

AU - Kong, Ah Ng Tony

AU - Conney, Allan H.

PY - 2006/6/1

Y1 - 2006/6/1

N2 - Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice. Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2). Results: Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33% in experiment 1 and 100% in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17% and 57% of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression. Conclusions: TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted.

AB - Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice. Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2). Results: Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33% in experiment 1 and 100% in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17% and 57% of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression. Conclusions: TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted.

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DO - 10.1158/1078-0432.CCR-05-2823

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SP - 3444

EP - 3451

JO - Clinical Cancer Research

JF - Clinical Cancer Research

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