title: Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases.
abstract: Lysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases. Activation of NADPH oxidase has been shown to play a mediating role in the signaling pathways by which LPA, as well as RANKL, promote osteolysis. In addition, there is reason to suspect that Nox4 activation is a mediator of the feed-forward mechanism whereby release of TGF-beta from bone matrix by osteolysis promotes expression of PTHrP in cancer cells, and thereby induces further osteolysis. Hence, measures which can down-regulate NADPH oxidase activity may have potential for slowing the expansion of osteolytic bone metastases in cancer patients. Phycocyanin and high-dose statins may have utility in this regard, and could be contemplated as complements to bisphosphonates or denosumab for the prevention and control of osteolytic lesions. Ingestion of omega-3-rich flaxseed or fish oil may also have potential for controlling osteolysis in cancer patients.
authors: Catalytic Longevity, 7831 Rush Rose Dr, Apt 316, Carlsbad, CA 92009, USA. markfmccarty@catalyticlongevity.org.
authors: Mark F
authors: MF
authors: McCarty
authors: Catalytic Longevity, 7831 Rush Rose Dr, Apt 316, Carlsbad, CA 92009, USA. jjdinicol@gmail.com.
authors: James
authors: J
authors: DiNicolantonio
keywords: NADPH oxidase; TGF-beta, phycocyanin; lysophosphatidic acid; osteolysis; statins