Akt- and CREB-mediated prostate cancer cell proliferation inhibition by nexrutine, a Phellodendron amurense extract

Gretchen E. Garcia, Arevalo Nicole, Shylesh Bhaskaran, Ashima Gupta, Natasha Kyprianouy, Addanki P. Kumar

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Evidence from epidemiological studies suggests that plant-based diets can reduce the risk of prostate cancer. However, very little information is available concerning the use of botanicals in preventing prostate cancer. As a first step toward developing botanicals as prostate cancer preventives, we examined the effect of Nexrutine on human prostate cancer cells. Nexrutine is a herbal extract developed from Phellodendron amurense. Phellodendron extracts have been used traditionally in Chinese medicine for hundreds of years as an anti-diarrheal, astringent, and anti-inflammatory agent. The present study investigated its potential antitumor effect on human prostate cancer cells.Our results suggest that it inhibits tumor cell proliferation through apoptosis induction and inhibition of cell survival signaling. The results of the present study indicate that Nexrutine treatment 1) inhibits the proliferation of both androgen-responsive and androgen-independent human prostate cancer cells through induction of apoptosis; 2) reduces levels of pAkt, phosphorylated cAMP response-binding protein (pCREB), and CREB DNA-binding activity; and 3) induces apoptosis in prostate cancer cells stably overexpressing Bcl-2. Further Akt kinase activity was reduced in cells treated with Nexrutine, and ectopic expression of myristoylated Akt protected from Nexrutine induced inhibition of proliferation, implicating a role for Akt signaling.

Original languageEnglish (US)
Pages (from-to)523-533
Number of pages11
Issue number6
StatePublished - 2006


  • Akt/CREB signaling
  • Bcl-2-independent apoptosis
  • CREB DNA binding
  • Herbal extracts
  • Nexrutine

ASJC Scopus subject areas

  • Cancer Research


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