BIRM [Biological Immune Response Modifier] is an extract from Kalanchoe gastonis-bonnieri, found in the Amazon forest of Ecuador [1] [3].
Nalakrats brought it to my attention. It can be purchased via Amazon.
There are only two PCa studies on PubMed. The first [2] was in 2003 from the University of Miami School of Medicine. The second [3] was published in 2016, i.e. after a gap of 13 years. Both studies were led by Dr. Bal Lokeshwar, who moved from Miami to Augusta University, GA in 2014. Perhaps there was a funding issue in Miami, but, clearly, Dr. Lokeshwar has retained an interest in BIRM. The paper was actually written by N. Shamaladevi, University of Miami, with co-authors from Japan & Ecuador.
In the interim, Dr. Lokeshwar's name appears on numerous papers, including two dozen PCa papers. (As you can see, I am trying to drum up interest in what is a little-known little-studied supplement. Lokeshwar has been involved in some interesting PCa studies.)
In the earlier study [2], "The cytotoxicity of BIRM in four human and one rat CaP cell line was evaluated". The four human cell lines are not named in the Abstract.
"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%."
In addition: "The in vivo efficacy of BIRM was evaluated in rats with subcutaneous tumor implants of Dunning EGFP-MAT LyLu cells." i.e. human cell lines were not used in the rat part of the study.
"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."
In the recent study:
"In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis. Exposing cells to BIRM did not affect the synthesis of AR and AR promoter activity but increased degradation of AR via proteasome-pathway."
i.e. while BIRM degraded AR, it did so more effectively when AR was active.
"BIRM caused destabilization of HSP90-AR association in LAPC-4 cells."
HSP90 is a heat shock protein. It acts as an AR chaperone, making the AR more difficult to target. If BIRM interferes with its chaperone duties, BIRM might be useful in therapies known to induce HSP90.
"BIRM dosed by oral gavage in mice bearing PC-3ML tumors showed selective efficacy on tumor growth before tumors are established but limited efficacy when treated on existing tumors."
That's a disappointment.
From the full text:
"BIRM is extensively used in Western
Hemisphere mainly as Herbal immune booster, as by th e
manufacturer (Ecua-BIRM Inc., Quito, EC and on their
website [WWW.EcuaBIRM.Com]. In addition, as per the
manufacturer of BIRM, this product has been dispensed
as a complementary medicine for ailments such as AIDS,
lupus, arthritis related psoriasis and various treatment refractory
cancers."
Unfortunately, PubMed has no supporting studies for BERM use under these conditions.
-Patrick
[1] en.wikipedia.org/wiki/Kalan...
[2] ncbi.nlm.nih.gov/pubmed/127...
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 DS1, Lokeshwar VB, Cevallos-Arellano E, Soloway MS, Lokeshwar BL.
Author information
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 (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).
CONCLUSION:
The plant extract BIRM contains antitumor compounds of Mr >or=3500 with potent antiproliferative activity in vitro and in vivo against prostate cancer cells.
PMID: 12734674 DOI: 10.1007/s00280-003-0612-1
[Indexed for MEDLINE]
[3] ncbi.nlm.nih.gov/pubmed/277...
FULL Text can be accessed.
Oncotarget. 2016 Dec 20;7(51):84201-84213. doi: 10.18632/oncotarget.12393.
The andean anticancer herbal product BIRM causes destabilization of androgen receptor and induces caspase-8 mediated-apoptosis in prostate cancer.
Shamaladevi N1, Araki S1,2, Lyn DA1, Ayyathurai R3, Gao J4, Lokeshwar VB5, Navarrete H6, Lokeshwar BL4.
Author information
Abstract
BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity. In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis. Exposing cells to BIRM did not affect the synthesis of AR and AR promoter activity but increased degradation of AR via proteasome-pathway. BIRM caused destabilization of HSP90-AR association in LAPC-4 cells. It induced apoptosis in PCa cells by activation of caspase-8 via death receptor and FADD-mediated pathways. A synthetic inhibitor of Caspase-8 cleavage (IETD-CHO) aborted BIRM-induced apoptosis. The effect of BIRM on AKT-mediated survival pathway in both AR+ and AR- negative (PC-3 and DU145) showed decreased levels of p-AKTser 473 in all PCa cell lines. BIRM dosed by oral gavage in mice bearing PC-3ML tumors showed selective efficacy on tumor growth; before tumors are established but limited efficacy when treated on existing tumors. Moreover, BIRM inhibited the LNCaP tumor generated by orthotropic implantation into dorsal prostate of nude mice. Partial purification of BIRM by liquid-liquid extraction and further fractionation by HPLC showed 4-fold increased specific activity on PCa cells. These results demonstrate a mechanistic basis of anti-tumor activity of the herbal extract BIRM.
KEYWORDS:
Anti-cancer herbal preparation; androgen receptor; caspase-8; chemoprevention; prostate cancer
PMID: 27705939 DOI: 10.18632/oncotarget.12393
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