Curcumin attenuates β-catenin signaling in prostate cancer cells through activation of protein kinase D1

Vasudha Sundram, Subhash Chauhan, Mara Ebeling, Meena Jaggi

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Prostate cancer is the most commonly diagnosed cancer affecting 1 in 6 males in the US. Understanding the molecular basis of prostate cancer progression can serve as a tool for early diagnosis and development of novel treatment strategies for this disease. Protein Kinase D1 (PKD1) is a multifunctional kinase that is highly expressed in normal prostate. The decreased expression of PKD1 has been associated with the progression of prostate cancer. Therefore, synthetic or natural products that regulate this signaling pathway can serve as novel therapeutic modalities for prostate cancer prevention and treatment. Curcumin, the active ingredient of turmeric, has shown anti-cancer properties via modulation of a number of different molecular pathways. Herein, we have demonstrated that curcumin activates PKD1, resulting in changes in β-catenin signaling by inhibiting nuclear β-catenin transcription activity and enhancing the levels of membrane β-catenin in prostate cancer cells. Modulation of these cellular events by curcumin correlated with decreased cell proliferation, colony formation and cell motility and enhanced cell-cell aggregation in prostate cancer cells. In addition, we have also revealed that inhibition of cell motility by curcumin is mediated by decreasing the levels of active cofilin, a downstream target of PKD1. The potent anti-cancer effects of curcumin in vitro were also reflected in a prostate cancer xenograft mouse model. The in vivo inhibition of tumor growth also correlated with enhanced membrane localization of β-catenin. Overall, our findings herein have revealed a novel molecular mechanism of curcumin action via the activation of PKD1 in prostate cancer cells.

Original languageEnglish (US)
Article numbere35368
JournalPloS one
Volume7
Issue number4
DOIs
StatePublished - Apr 16 2012

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Catenins
Curcumin
curcumin
prostatic neoplasms
protein kinases
Protein Kinases
Prostatic Neoplasms
Chemical activation
Cells
cell movement
Modulation
Actin Depolymerizing Factors
neoplasms
Cell Movement
Membranes
Neoplasms
Cell proliferation
Transcription
Biological Products
Heterografts

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Curcumin attenuates β-catenin signaling in prostate cancer cells through activation of protein kinase D1. / Sundram, Vasudha; Chauhan, Subhash; Ebeling, Mara; Jaggi, Meena.

In: PloS one, Vol. 7, No. 4, e35368, 16.04.2012.

Research output: Contribution to journalArticle

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