A lipoxygenase inhibitor in breast cancer brain metastases

Abstract

The complication of multiple brain metastases in breast cancer patients is a life threatening condition with limited success following standard therapies. The arachidonate lipoxygenase pathway appears to play a role in brain tumor growth as well as inhibition of apoptosis in in-vitro studies. The down regulation of these arachidonate lipoxygenase growth stimulating products therefore appeared to be a worthwhile consideration for testing in brain metastases not responding to standard therapy. Boswellia serrata, a lipoxygenase inhibitor was applied for this inhibition. Multiple brain metastases were successfully reversed using this method in a breast cancer patient who had not shown improvement after standard therapy. The results suggest a potential new area of therapy for breast cancer patients with brain metastases that may be useful as an adjuvant to our standard therapy.

5-Lipoxygenase and 5-Lipoxygenase-Activating Protein Gene Polymorphisms, Dietary Linoleic Acid, and Risk for Breast Cancer

“…One possible mechanism involves the arachidonic acid 5-lipoxygenase pathway metabolites that have been found to promote tumorigenesis in breast tissue (21)(22)(23) and influence breast cancer prognosis and metastases (19,24). Among humans, however, a meta-analysis of 45 epidemiologic studies did not support a positive association between n-6 polyunsaturated fatty acid and breast cancer risk (25).…”

“…In breast cancer, 5-lipoxygenase and 5-lipoxygenase-activating protein have been found to be overexpressed in tumor tissue (19) and have been related to cancer prognosis and survival (20). Disruption of the 5-lipoxygenase signaling pathway mediates growth arrest and apoptosis in breast cancer cells (21)(22)(23), and inhibits breast cancer metastases (24).…”

Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

“…have been shown to possess anti-bacterial, anti-fungal [7], anti-carcinogenic [8], and anti-neoplastic [9,10] properties. Clinically, extracts from the resin have been shown to reduce the peritumoral edema in glioblastoma patients [9] and reverse multiple brain metastases in a breast cancer patient [11]. These results suggest that resins from Boswellia sp .…”

Critical Dietary Factors in Cancer Chemoprevention

“…Meanwhile, the same group has disclosed the total synthesis of guttiferone A in a similar way (Horeischi et al 2014 Much of the chemopreventive activity of garcinol (1) can be assigned to its radical scavenging properties against superoxide anions, hydroxyl radicals, and methyl radicals and, thus, protection of cellular components from lethal damage. Inhibition of 5-LOX activity seems to be a particularly efficient strategy to combat metastases, and COX-2 catalysed PGE2 formation is often related with enhanced metastasis by upregulation of matrix metalloproteinases such as MMP-2 (Flavin 2007;Ito et al 2004). In addition, garcinol also inhibited protein glycation .…”