Anti-prostate cancer activity of a β-carboline alkaloid enriched extract from Rauwolfia vomitoria

  • Authors:
    • D. L. Bemis
    • J. L. Capodice
    • P. Gorroochurn
    • A. E. Katz
    • R. Buttyan
  • View Affiliations

  • Published online on: November 1, 2006     https://doi.org/10.3892/ijo.29.5.1065
  • Pages: 1065-1073
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

The tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a variety of ailments. A bioactive β-carboline alkaloid, alstonine, present in this extract was previously shown to have anti-cancer activity against cancer cell lines. This study considers the potential anti-prostate cancer activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract standardized for β-carboline alkaloids was tested for ability to influence the growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay was used to measure cell growth, and cell cycle analyses were conducted with flow cytometry. Western blot detection of PARP cleavage and accumulation of cells containing sub-genomic DNA indicated induction of apoptosis. Pathway specific microarray analyses were utilized to identify the effect of Rauwolfia extract on the expression of 225 genes. Mice xenografted with LNCaP cells were treated with the extract or placebo control, and tumor growth was measured for 5 weeks. The effects of the extract on xenografted tumor cell proliferation and apoptosis were measured by in situ BrdU incorporation and TUNEL staining. Rauwolfia extract decreased in vitro cell growth in a dose-dependent manner (p<0.001) and induced the accumulation of G1 phase cells. PARP cleavage demonstrated that apoptosis was induced only at the highest concentration tested (500 µg/ml) which was confirmed by detection of cells containing sub-genomic DNA. The expression of genes associated with DNA damage signaling pathway was up-regulated by Rauwolfia treatment, including that of GADD153 and MDG. The expression of a few cell cycle genes (p21, cyclin D1 and E2F1) was also modulated. These alterations were confirmed by RT-PCR. Tumor volumes were decreased by 60%, 70% and 58% in the groups fed the 75, 37.5 or 7.5 mg/kg Rauwolfia, respectively (Kruskal-Wallis test, p<0.001). The Rauwolfia vomitoria extract significantly suppressed the growth and cell cycle progression of LNCaP cells, in vitro and in vivo.

Related Articles

Journal Cover

November 2006
Volume 29 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Bemis, D.L., Capodice, J.L., Gorroochurn, P., Katz, A.E., & Buttyan, R. (2006). Anti-prostate cancer activity of a β-carboline alkaloid enriched extract from Rauwolfia vomitoria. International Journal of Oncology, 29, 1065-1073. https://doi.org/10.3892/ijo.29.5.1065
MLA
Bemis, D. L., Capodice, J. L., Gorroochurn, P., Katz, A. E., Buttyan, R."Anti-prostate cancer activity of a β-carboline alkaloid enriched extract from Rauwolfia vomitoria". International Journal of Oncology 29.5 (2006): 1065-1073.
Chicago
Bemis, D. L., Capodice, J. L., Gorroochurn, P., Katz, A. E., Buttyan, R."Anti-prostate cancer activity of a β-carboline alkaloid enriched extract from Rauwolfia vomitoria". International Journal of Oncology 29, no. 5 (2006): 1065-1073. https://doi.org/10.3892/ijo.29.5.1065