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Healthcare 2016, 4(3), 60; doi:10.3390/healthcare4030060

Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases

Catalytic Longevity, 7831 Rush Rose Dr, Apt 316, Carlsbad, CA 92009, USA
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Academic Editor: Sampath Parthasarathy
Received: 19 July 2016 / Revised: 11 August 2016 / Accepted: 22 August 2016 / Published: 25 August 2016
View Full-Text   |   Download PDF [220 KB, uploaded 25 August 2016]

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. View Full-Text
Keywords: lysophosphatidic acid; osteolysis; NADPH oxidase; TGF-beta, phycocyanin; statins lysophosphatidic acid; osteolysis; NADPH oxidase; TGF-beta, phycocyanin; statins
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

McCarty, M.F.; DiNicolantonio, J. Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases. Healthcare 2016, 4, 60.

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