- Cancer Chemother Pharmacol. 2003 Jul;52(1):59-66. Epub 2003 May 7.
An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis.
Dandekar DS, Lokeshwar VB, Cevallos-Arellano E, Soloway MS, Lokeshwar BL.
Department of Urology, McKnight Vision Research Building, University of Miami School of Medicine, Miami, Florida 33101, USA.
Poor efficacy of conventional chemotherapeutic drugs against metastatic
hormone-refractory prostate cancer (CaP) drives patients to try
"alternative medicine". The antitumor activity of one such agent,
"BIRM" (biological immune response modulator; "Simple Ecuadorian Oral
Solution: an extract of an Amazonian plant"), was characterized in
vitro and in vivo using established CaP cell lines and a tumor model.
METHODS: The cytotoxicity of BIRM in four human and one rat CaP cell
line was evaluated using cell proliferation-inhibition and clonogenic
survival assays. BIRM-induced apoptosis, alterations in cell cycle
phase progression and inhibition of the extracellular matrix-degrading
enzyme hyaluronidase were also investigated in these cells. The in vivo
efficacy of BIRM was evaluated in rats with subcutaneous tumor implants
of Dunning EGFP-MAT LyLu cells. The active species in BIRM were
characterized by gel filtration chromatography.
RESULTS: BIRM inhibited
cell proliferation and clonogenic growth of the CaP cells (IC(50) about
8.0 microl/ml). It increased cell accumulation in the G(0)/G(1) phase
by 33.8% and decreased the proportion of cells in S phase by 54.6%.
Apoptotic cell death in BIRM-treated cells was associated with
activation of cell death-associated caspases. BIRM inhibited the
activity of hyaluronidase, a hyaluronic acid-degrading enzyme, at 1
microl/ml. Treatment of MAT LyLu tumor-bearing rats with BIRM by oral
gavage resulted in a significant decrease in tumor incidence (50%),
tumor growth rate (18.6+/-1.3 days for 1 cc tumor growth in control
rats and 25.7+/-2.6 days in BIRM-treated rats), and only one out of six
BIRM-treated rats versus four out of six in the control group developed
lung metastasis. Three active ingredients in BIRM with a relative
molecular mass (Mr) of >or=3500 were identified by
ultracentrifugation and gel filtration chromatography and were found to
be resistant to proteinase and heat (100 degrees C).
plant extract BIRM contains antitumor compounds of Mr >or=3500 with
potent antiproliferative activity in vitro and in vivo against prostate