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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics

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Research Article

Wedelolactone, an anti-inflammatory botanical, interrupts c-Myc oncogenic signaling and synergizes with enzalutamide to induce apoptosis in prostate cancer cells

Sivalokanathan Sarveswaran, Ritisha Ghosh, Rujul Parikh and Jagadananda Ghosh
Sivalokanathan Sarveswaran
Vattikuti Urology Institute, Henry Ford Health System
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Ritisha Ghosh
Vattikuti Urology Institute, Henry Ford Health System
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Rujul Parikh
Vattikuti Urology Institute, Henry Ford Health System
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Jagadananda Ghosh
Vattikuti Urology Institute, Henry Ford Health System
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  • For correspondence: jghosh1@hfhs.org
DOI: 10.1158/1535-7163.MCT-15-0861
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Abstract

The c-Myc gene encodes an oncoprotein transcription factor which is frequently up-regulated in almost all cancer types, and is the subject of intense investigation for management of cancer because of its pleiotropic effects controlling a spectrum of cellular functions. However, due of its non-enzymatic nature, development of suitable strategies to block its protein-protein or protein-DNA interaction is challenging. Thus, c-Myc has been recognized as an elusive molecular target for cancer control and various approaches are in development to inhibit c-Myc-transcriptional activity. We observed that wedelolactone (WDL), an anti-inflammatory botanical compound, severely down-regulates the expression of c-Myc mRNA in prostate cancer cells. Moreover, WDL dramatically decreases the protein level, nuclear localization, DNA-binding, and transcriptional activities of c-Myc. c-Myc is a transforming oncogene widely expressed in prostate cancer cells and is critical for maintaining their transformed phenotype. Interestingly, WDL was found to strongly affect the viability of Myc-activated prostate cancer cells, and completely blocks their invasion as well as soft-agar colony-formation in vitro. WDL was also found to down-regulate c-Myc in vivo in nude mice xenografts. Moreover, WDL synergizes with enzalutamide to decrease the viability of androgen-sensitive prostate cancer cells via induction of apoptosis. These findings reveal a novel anticancer mechanism of the natural compound, WDL, and suggest that the oncogenic function of c-Myc in prostate cancer cells can be effectively down-regulated by WDL for the development of a new therapeutic strategy against Myc-driven prostate cancer.

  • Received October 22, 2015.
  • Revision received July 1, 2016.
  • Accepted July 19, 2016.
  • Copyright {copyright, serif}2016, American Association for Cancer Research.
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Published OnlineFirst July 29, 2016
doi: 10.1158/1535-7163.MCT-15-0861

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Wedelolactone, an anti-inflammatory botanical, interrupts c-Myc oncogenic signaling and synergizes with enzalutamide to induce apoptosis in prostate cancer cells
Sivalokanathan Sarveswaran, Ritisha Ghosh, Rujul Parikh and Jagadananda Ghosh
Mol Cancer Ther July 29 2016 DOI: 10.1158/1535-7163.MCT-15-0861

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Wedelolactone, an anti-inflammatory botanical, interrupts c-Myc oncogenic signaling and synergizes with enzalutamide to induce apoptosis in prostate cancer cells
Sivalokanathan Sarveswaran, Ritisha Ghosh, Rujul Parikh and Jagadananda Ghosh
Mol Cancer Ther July 29 2016 DOI: 10.1158/1535-7163.MCT-15-0861
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Copyright 2016 by the American Association for Cancer Research.

Molecular Cancer Therapeutics
eISSN: 1538-8514
ISSN: 1535-7163

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