An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis

Purpose: 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 (IC₅₀ about 8.0 μl/ml). It increased cell accumulation in the G₀/G₁ 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 μl/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 ≥3500 were identified by ultracentrifugation and gel filtration chromatography and were found to be resistant to proteinase and heat (100°C). Conclusion: The plant extract BIRM contains antitumor compounds of Mr ≥3500 with potent antiproliferative activity in vitro and in vivo against prostate cancer cells.