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

Devendra S. Dandekar, Vinata B Lokeshwar, Edwin Cevallos-Arellano, Mark S. Soloway, Balakrishna L Lokeshwar

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume52
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

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Plant Extracts
Tumors
Prostatic Neoplasms
Rats
Neoplasm Metastasis
Cells
Growth
Hyaluronoglucosaminidase
Cell proliferation
Cell death
Chromatography
Neoplasms
Bearings (structural)
Gel Chromatography
Gels
Rat control
Cell Death
Cell Proliferation
Molecular mass
Cell Cycle Resting Phase

Keywords

  • Apoptosis
  • Chemoprevention
  • Invasion and metastasis
  • Natural herbal anticancer products
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis. / Dandekar, Devendra S.; Lokeshwar, Vinata B; Cevallos-Arellano, Edwin; Soloway, Mark S.; Lokeshwar, Balakrishna L.

In: Cancer Chemotherapy and Pharmacology, Vol. 52, No. 1, 01.07.2003, p. 59-66.

Research output: Contribution to journalArticle

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abstract = "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.",
keywords = "Apoptosis, Chemoprevention, Invasion and metastasis, Natural herbal anticancer products, Prostate cancer",
author = "Dandekar, {Devendra S.} and Lokeshwar, {Vinata B} and Edwin Cevallos-Arellano and Soloway, {Mark S.} and Lokeshwar, {Balakrishna L}",
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AU - Dandekar, Devendra S.

AU - Lokeshwar, Vinata B

AU - Cevallos-Arellano, Edwin

AU - Soloway, Mark S.

AU - Lokeshwar, Balakrishna L

PY - 2003/7/1

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N2 - 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.

AB - 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.

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KW - Chemoprevention

KW - Invasion and metastasis

KW - Natural herbal anticancer products

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