Resin from Boswellia, a family of flowering shrubs & trees, has been used for medicinal purposes for many centuries. It is employed in Ayurvedic medicine. Frankincense, as mentioned in the Bible, is extracted from Boswellia sacra, but there are other species of Boswellia that provide useful resin.
Terpenes are substances found in a variety of shrubs & trees (think turpentine, which contain terpenes). They have a protective function.
Boswellic acids are triterpenes extracted from Boswellia. Acetyl-keto-beta-boswellic acid (AKBA) is the form most studied in PCa.
[1] AKBA. "Acetyl-keto-β-boswellic acid (AKBA), a triterpenoid isolated from Boswellia carterri Birdw and Boswellia serrata, has been found to inhibit tumor cell growth and to induce apoptosis."
[1a] (2008 - U.S.)
"The apoptotic effects and the mechanisms of action of AKBA were studied in LNCaP and PC-3 human prostate cancer cells. AKBA induced apoptosis in both cell lines at concentrations above 10 μg/mL."
"In this study, we found that AKBA induced apoptosis through the death receptor–mediated pathway in prostate cancer cells."
(The full text is a lot more technical than that - be warned!)
[1b] (2008 - China)
"Inhibitory effect of acetyl-11-keto-beta-boswellic acid on androgen receptor ..."
"Androgen receptor (AR)-mediated signaling is crucial for the development and progression of prostate cancer (PCa). Naturally occurring phytochemicals that target the AR signaling offer significant protection against this disease. Acetyl-11-keto-beta-boswellic acid (AKBA), a compound isolated from the gum-resin of Boswellia carterii, caused G1-phase cell cycle arrest ..." i.e. cell division was halted during one of its phases.
"AKBA-mediated cellular proliferation inhibition was associated with a decrease of AR expression ..."
[1c] (2009 - China)
"The role of angiogenesis in tumor growth and metastasis is well established. Identification of a small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we showed that acetyl-11-keto-β-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA) after solid tumors reached ∼100 mm3 (n = 5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation ..."
[2] PCa chronically activates pro-survival NF-kB. Of the many proteins produced upon NF-kB activation, there are the enzymes that act on the fatty acid arachidonic acid, stored in the lipid rafts of the cells. Not only the familiar cyclooxygenase [COX-1 & COX-2] enzymes, but also the lipoxygenase [LOX] enzymes. The ensuing metabolic cascade is a bit of a nightmare, in terms of controling proliferation.
[2a] 5-lipoxygenase [5-LOX aka ALOX5] from Wikipedia:
"Aberrant expression of ALOX5 is seen in various types of human cancer tumors in vivo as well as in various types of human cancer cell lines in vitro; these tumors and cell lines include those of the pancreas, prostate and colon. ALOX5 products, particularly 5-hydroxyeicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, promote the proliferation of these ALOX5 aberrantly expressing tumor cell lines suggesting that ALOX5 acts as a pro-malignancy factor for them and by extension their parent tumors."
Although 5-LOX metabolizes the omega-6 arachidonic acid [AA], it can also metabolize the marine omega-3 fatty acids EPA & DHA. The omega-3 metabolites are more benign. In fact the AA:(EPA+DHA) ratio is very important. In general, when AA is dominant, the inflammatory response is out of proportion to the stimulus.
But in PCa, the stimulus is always there: chronic NF-kB activation.
[2b] (1997 - our very own Dr. Myers, while he was at UVA)
"Arachidonic acid stimulates prostate cancer cell growth: critical role of 5-lipoxygenase."
AA actually represents inflammatory & proliferation potential. It needs the enzymes to activate that potential.
"Selective blockade of the different metabolic pathways of arachidonic acid (e.g. ibuprofen for cyclooxygenase, SKF-525A for cytochrome P-450, baicalein and BHPP for 12-lipoxygenase, AA861 and MK886 for 5-lipoxygenase, etc.) revealed that the growth stimulatory effect of arachidonic acid is inhibited by the 5-lipoxygenase specific inhibitors, AA861 and MK886, but not by others."
Cell growth here is linked to the 5-HETE metabolites:
"Addition of the eicosatetraenoid products of 5-lipoxygenase (5-HETEs) showed stimulation of prostate cancer cell growth similar to that of arachidonic acid, whereas the leukotrienes were ineffective. Moreover, the 5-series of eicosatetraenoids could reverse the growth inhibitory effect of MK886. Finally, prostate cancer cells fed with arachidonic acid showed a dramatic increase in the production of 5-HETEs which is effectively blocked by MK886. These experimental observations suggest that arachidonic acid needs to be metabolized through the 5-lipoxygenase pathway to produce 5-HETE series of eicosatetraenoids for its growth stimulatory effects on human prostate cancer cells."
[2c] The 5-LOXIN product.
"The novel anti-inflammatory properties of the gum resin derived from Boswellia serrata, also known as Salai guggal in Ayurvedic medicine, are well recognized and highly recommended for human consumption. The active constituents of the gum resin are boswellic acids (BAs). Among the BAs, AKBA potently inhibits 5-lipoxygenase product formation with an IC(50) of 1.5 m muM. We developed a novel Boswellia serrata extract (5-Loxin(R)) enriched with 30% AKBA (US Patent 2004/0073060A1)."
[2d] 5-LOXIN (Boswellia Serrata Extract - 30% AKBA)
[2e] AprèsFlex® (Boswellia serrata) extract (gum resin) [std. to 20% 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) (20 mg)] LEF used to sell 5-LOXIN but switched to AprèsFlex
-Patrick
[1a] cancerres.aacrjournals.org/...
[1b] ncbi.nlm.nih.gov/pubmed/184...
[1c] cancerres.aacrjournals.org/...
[2] swansonvitamins.com/swanson...
[2a] en.wikipedia.org/wiki/Arach...
[2b] ncbi.nlm.nih.gov/pubmed/919...
[2c] ncbi.nlm.nih.gov/pubmed/200...
