Plumbagin inhibits prostate carcinogenesis in intact and castrated PTEN knockout mice via targeting PKCε, Stat3, and epithelial-to-mesenchymal transition markers

Bilal Hafeez, Joseph W. Fischer, Ashok Singh, Weixiong Zhong, Ala Mustafa, Louise Meske, Mohammad Ozair Sheikhani, Ajit Kumar Verma

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4+) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.

Original languageEnglish (US)
Pages (from-to)375-386
Number of pages12
JournalCancer Prevention Research
Volume8
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Epithelial-Mesenchymal Transition
Knockout Mice
Prostate
Prostatic Neoplasms
Carcinogenesis
Gastropoda
Vimentin
Prostatic Intraepithelial Neoplasia
Naphthoquinones
Neoplasms
Second Primary Neoplasms
Sequence Deletion
Castration
Medicinal Plants
plumbagin
Adenocarcinoma
Epithelium
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Plumbagin inhibits prostate carcinogenesis in intact and castrated PTEN knockout mice via targeting PKCε, Stat3, and epithelial-to-mesenchymal transition markers. / Hafeez, Bilal; Fischer, Joseph W.; Singh, Ashok; Zhong, Weixiong; Mustafa, Ala; Meske, Louise; Sheikhani, Mohammad Ozair; Verma, Ajit Kumar.

In: Cancer Prevention Research, Vol. 8, No. 5, 01.05.2015, p. 375-386.

Research output: Contribution to journalArticle

Hafeez, Bilal ; Fischer, Joseph W. ; Singh, Ashok ; Zhong, Weixiong ; Mustafa, Ala ; Meske, Louise ; Sheikhani, Mohammad Ozair ; Verma, Ajit Kumar. / Plumbagin inhibits prostate carcinogenesis in intact and castrated PTEN knockout mice via targeting PKCε, Stat3, and epithelial-to-mesenchymal transition markers. In: Cancer Prevention Research. 2015 ; Vol. 8, No. 5. pp. 375-386.
@article{fb8db8ff40f64e47a2a8e58dec3643fc,
title = "Plumbagin inhibits prostate carcinogenesis in intact and castrated PTEN knockout mice via targeting PKCε, Stat3, and epithelial-to-mesenchymal transition markers",
abstract = "Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4+) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.",
author = "Bilal Hafeez and Fischer, {Joseph W.} and Ashok Singh and Weixiong Zhong and Ala Mustafa and Louise Meske and Sheikhani, {Mohammad Ozair} and Verma, {Ajit Kumar}",
year = "2015",
month = "5",
day = "1",
doi = "10.1158/1940-6207.CAPR-14-0231",
language = "English (US)",
volume = "8",
pages = "375--386",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Plumbagin inhibits prostate carcinogenesis in intact and castrated PTEN knockout mice via targeting PKCε, Stat3, and epithelial-to-mesenchymal transition markers

AU - Hafeez, Bilal

AU - Fischer, Joseph W.

AU - Singh, Ashok

AU - Zhong, Weixiong

AU - Mustafa, Ala

AU - Meske, Louise

AU - Sheikhani, Mohammad Ozair

AU - Verma, Ajit Kumar

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4+) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.

AB - Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4+) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=84942522244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942522244&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-14-0231

DO - 10.1158/1940-6207.CAPR-14-0231

M3 - Article

VL - 8

SP - 375

EP - 386

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 5

ER -