Studying Rac1-Induced Tumorigenesis Suggests Antioxidants May Help Prevent and Treat Kaposi’s Sarcoma

Abstract

Evaluation of: Ma Q, Cavallin LE, Yan B et al.: Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi’s sarcoma. Proc. Natl Acad. Sci. USA 106, 8683–8688 (2009). The development of Kaposi’s sarcoma (KS) is preceded by the upregulation of several key gene products of human herpesvirus 8/Kaposi’s sarcoma-associated herpesvirus. Some of these virally-encoded proteins are cellular homologs of oncogenes that play a critical role in cell-cycle regulation and apoptosis. Among these, the viral G-protein-coupled receptor, when constitutively activated, leads to robust signaling through the phosphotidyl-inositol-3-kinase pathway, thereby promoting cellular growth, transformation, angiogenesis and anti-apoptosis. Importantly, recent evidence suggests that activation of this complex cellular machinery downstream of the viral G-protein-coupled receptor occurs, at least in part, through the activation of the small G-protein, Rac1. Building upon this, Ma and colleagues describe their development of a mouse model where constitutively active Rac1 leads to the formation of KS-like tumors. Furthermore, it appears that Rac1 signaling leads to reactive oxygen species formation, which appears to be the major driver of tumorigenesis in this model. The potential therapeutic implications of these findings are the incorporation of reactive oxygen species-scavenging agents, such as N-acetyl-cysteine, into the treatment armamentarium for KS. In addition, these agents may be equally or more important in the prevention of KS development in at-risk populations.

Keywords:

• angiogenesis
• antioxidant
• GTPase
• HHV-8
• Kaposi’s sarcoma
• KSHV
• mouse
• N-acetyl-cysteine
• Rac1
• vGPCR

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Funding

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.