Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 16 No.
3 • March 2013
Killing Prostate Cancer Cells
Inhibition of LOX-5 Triggers Massive Dying Off of Human Prostate Cancer Cells
An early (1998) paper described how arachidonic acid, an omega-6 fatty acid, stimulates proliferation of prostate cancer cells through its metabolite 5-HETE, produced by the action of 5-lipoxygenase. They refer to multiple studies that have suggested a role for arachidonic acid and its precursor, linoleic acid, in prostate cancer growth and metastasis. In their paper, the authors show that 5-HETE is also a potent survival factor for human prostate cancer cells. They showed that, by inhibiting 5-lipoxygenase, 5-HETE production was completely prevented and that this resulted in massive apoptosis (programmed cell death) in both hormone-responsive (LNCaP) and -nonresponsive (PC3) human prostate cancer cells. The apoptosis was blocked by the thiol antioxidant N-acetylcysteine. These results, the authors state, identifies a possible mechanism by which high dietary fat can promote the progression of prostate cancer.
A more recent (2007) paper follows up on these earlier findings by reporting on the use of 5-LOX inhibitors to block the conversion of arachidonic acid to 5-LOX products associated with various disorders, including osteoporosis and cancers (e.g., prostate, pancreas and breast), as well as atherosclerosis, heart attack, and stroke. The author describes many natural products that act as 5-LOX inhibitors or inhibitors of 5-LOX products, including nordihydroguaiaretic acid (NDGA), caffeic acid, quercetin, luteolin, silibinin, curcumin, gingerols (derived from ginger), rosmarinic acid, and resveratrol. Also, see
(below) on benfotiamine.
Boswellic acids have also been reported as inhibitors of 5-LOX, have potent anti-inflammatory activity, and have been extensively investigated for their activity against tumor cells and in cancer chemoprevention.
- Ghosh and Myers. Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proc Nat Acad Sci USA. 95:13182-7 (1998).
- Werz. Inhibition of 5-lipoxygenase product synthesis by natural compounds of plant origin. Planta Med. 73:1331-57 (2007).
- Banno et al. Anti-inflammatory activities of the triterpene acids from the resin of Boswellia carteri. Jnbsp;Ethnopharmacol. 107:249-53 (2006).