Combination treatment of prostate cancer cell lines with bioactive soy isoflavones and perifosine causes increased growth arrest and/or apoptosis

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Abstract

Purpose: To determine whether targeting the androgen receptor (AR) and Akt pathways using a combination of genistein combined polysaccharide (GCP) and perifosine is more effective at inducing growth arrest/apoptosis in prostate cancer cells compared with treatment with GCP or perifosine as single agents. Experimental Design: The effect of GCP and perifosine treatment was assessed in five prostate cancer cell lines: LNCaP (androgen sensitive), LNCaP-R273H, C4-2, Cds1, and PC3 (androgen insensitive). A clonogenic assay assessed the long-term effects on cell growth and survival. Flow cytometry and Western blot analysis of poly(ADP)ribose polymerase cleavage were used to assess short-term effects. Preliminary studies to investigate mechanism of action included Western blot for P-Akt, Akt, P-p70S6K, p70S6K, p53, and p21; prostate-specific antigen analysis; and the use of myristoylated Akt and AR-specific small interfering RNA. Results: Combination treatment with GCP and perifosine caused a decrease in clonogenic potential in all cell lines. In short-term assays, growth arrest was observed in the majority of cell lines, as well as increased inhibition of Akt activity and induction of p21 expression. Increased apoptosis was only observed in LNCaP. Knockdown of AR caused a further increase in apoptosis. Conclusion: Combination treatment with GCP and perifosine targets the Akt pathway in the majority of the prostate cancer cell lines and causes increased inhibition of cell growth and clonogenicity. In LNCaP, combination treatment targets both the Akt and AR pathways and causes increased apoptosis. These data warrant clinical validation in prostate cancer patients.

Original languageEnglish (US)
Pages (from-to)6204-6216
Number of pages13
JournalClinical Cancer Research
Volume13
Issue number20
DOIs
StatePublished - Oct 15 2007

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Isoflavones
Androgen Receptors
Prostatic Neoplasms
Apoptosis
Cell Line
70-kDa Ribosomal Protein S6 Kinases
Growth
Androgens
Western Blotting
Therapeutics
Poly(ADP-ribose) Polymerases
Prostate-Specific Antigen
Small Interfering RNA
Cell Survival
Flow Cytometry
Research Design
genistein combined polysaccharide
perifosine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{78def77989da40f19d2f5f7eaec79cee,
title = "Combination treatment of prostate cancer cell lines with bioactive soy isoflavones and perifosine causes increased growth arrest and/or apoptosis",
abstract = "Purpose: To determine whether targeting the androgen receptor (AR) and Akt pathways using a combination of genistein combined polysaccharide (GCP) and perifosine is more effective at inducing growth arrest/apoptosis in prostate cancer cells compared with treatment with GCP or perifosine as single agents. Experimental Design: The effect of GCP and perifosine treatment was assessed in five prostate cancer cell lines: LNCaP (androgen sensitive), LNCaP-R273H, C4-2, Cds1, and PC3 (androgen insensitive). A clonogenic assay assessed the long-term effects on cell growth and survival. Flow cytometry and Western blot analysis of poly(ADP)ribose polymerase cleavage were used to assess short-term effects. Preliminary studies to investigate mechanism of action included Western blot for P-Akt, Akt, P-p70S6K, p70S6K, p53, and p21; prostate-specific antigen analysis; and the use of myristoylated Akt and AR-specific small interfering RNA. Results: Combination treatment with GCP and perifosine caused a decrease in clonogenic potential in all cell lines. In short-term assays, growth arrest was observed in the majority of cell lines, as well as increased inhibition of Akt activity and induction of p21 expression. Increased apoptosis was only observed in LNCaP. Knockdown of AR caused a further increase in apoptosis. Conclusion: Combination treatment with GCP and perifosine targets the Akt pathway in the majority of the prostate cancer cell lines and causes increased inhibition of cell growth and clonogenicity. In LNCaP, combination treatment targets both the Akt and AR pathways and causes increased apoptosis. These data warrant clinical validation in prostate cancer patients.",
author = "Vinall, {Ruth Louise} and Kimberley Hwa and Ghosh, {Paramita M} and Chong-Xian Pan and Lara, {Primo N} and {deVere White}, {Ralph W}",
year = "2007",
month = "10",
day = "15",
doi = "10.1158/1078-0432.CCR-07-0600",
language = "English (US)",
volume = "13",
pages = "6204--6216",
journal = "Clinical Cancer Research",
issn = "1078-0432",
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TY - JOUR

T1 - Combination treatment of prostate cancer cell lines with bioactive soy isoflavones and perifosine causes increased growth arrest and/or apoptosis

AU - Vinall, Ruth Louise

AU - Hwa, Kimberley

AU - Ghosh, Paramita M

AU - Pan, Chong-Xian

AU - Lara, Primo N

AU - deVere White, Ralph W

PY - 2007/10/15

Y1 - 2007/10/15

N2 - Purpose: To determine whether targeting the androgen receptor (AR) and Akt pathways using a combination of genistein combined polysaccharide (GCP) and perifosine is more effective at inducing growth arrest/apoptosis in prostate cancer cells compared with treatment with GCP or perifosine as single agents. Experimental Design: The effect of GCP and perifosine treatment was assessed in five prostate cancer cell lines: LNCaP (androgen sensitive), LNCaP-R273H, C4-2, Cds1, and PC3 (androgen insensitive). A clonogenic assay assessed the long-term effects on cell growth and survival. Flow cytometry and Western blot analysis of poly(ADP)ribose polymerase cleavage were used to assess short-term effects. Preliminary studies to investigate mechanism of action included Western blot for P-Akt, Akt, P-p70S6K, p70S6K, p53, and p21; prostate-specific antigen analysis; and the use of myristoylated Akt and AR-specific small interfering RNA. Results: Combination treatment with GCP and perifosine caused a decrease in clonogenic potential in all cell lines. In short-term assays, growth arrest was observed in the majority of cell lines, as well as increased inhibition of Akt activity and induction of p21 expression. Increased apoptosis was only observed in LNCaP. Knockdown of AR caused a further increase in apoptosis. Conclusion: Combination treatment with GCP and perifosine targets the Akt pathway in the majority of the prostate cancer cell lines and causes increased inhibition of cell growth and clonogenicity. In LNCaP, combination treatment targets both the Akt and AR pathways and causes increased apoptosis. These data warrant clinical validation in prostate cancer patients.

AB - Purpose: To determine whether targeting the androgen receptor (AR) and Akt pathways using a combination of genistein combined polysaccharide (GCP) and perifosine is more effective at inducing growth arrest/apoptosis in prostate cancer cells compared with treatment with GCP or perifosine as single agents. Experimental Design: The effect of GCP and perifosine treatment was assessed in five prostate cancer cell lines: LNCaP (androgen sensitive), LNCaP-R273H, C4-2, Cds1, and PC3 (androgen insensitive). A clonogenic assay assessed the long-term effects on cell growth and survival. Flow cytometry and Western blot analysis of poly(ADP)ribose polymerase cleavage were used to assess short-term effects. Preliminary studies to investigate mechanism of action included Western blot for P-Akt, Akt, P-p70S6K, p70S6K, p53, and p21; prostate-specific antigen analysis; and the use of myristoylated Akt and AR-specific small interfering RNA. Results: Combination treatment with GCP and perifosine caused a decrease in clonogenic potential in all cell lines. In short-term assays, growth arrest was observed in the majority of cell lines, as well as increased inhibition of Akt activity and induction of p21 expression. Increased apoptosis was only observed in LNCaP. Knockdown of AR caused a further increase in apoptosis. Conclusion: Combination treatment with GCP and perifosine targets the Akt pathway in the majority of the prostate cancer cell lines and causes increased inhibition of cell growth and clonogenicity. In LNCaP, combination treatment targets both the Akt and AR pathways and causes increased apoptosis. These data warrant clinical validation in prostate cancer patients.

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U2 - 10.1158/1078-0432.CCR-07-0600

DO - 10.1158/1078-0432.CCR-07-0600

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AN - SCOPUS:35948988138

VL - 13

SP - 6204

EP - 6216

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 20

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