Molecular targets of cancer cachexia: opportunities for pharmanutritional approaches
Journal Contribution ResearchOnline@JCUAbstract
Cancer cachexia is a complex syndrome of progressive weight loss especially devastating to skeletal muscle and adipose tissue. In about 30% of cancer patients, cachexia is the most common cause of death. Often cachexia is accompanied with loss of appetite, inflammation and insulin resistance. Several inflammatory cytokines including Tumor Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6) are known to be involved in cachexia. Besides the humoral factors, the tumoral factors such as Proteolysis Inducing Factor (PIF) play a role in inducing cachexia. Recently, our laboratory discovered that Myostatin, a Transforming Growth Factor-β (TGF-β) superfamily member, is abundantly secreted by C26 tumor cells. Previously others and our laboratory have established Myostatin as a pro-cachectic factor inducing muscle wasting through up-regulation of muscle-specific E3 ligases, Atrogin-1 and MuRF1, and enhanced activity of the ubiquitin-proteasome pathway. Myostatin has also been shown to induce Reactive Oxygen Species (ROS), TNF-α and IL-6. Collectively, these results indicate that Myostatin is a potential target of cancer cachexia and antagonism of Myostatin would be beneficial during cancer cachexia. On the nutrition front, nutrients like Omega-3 fatty acids, Leucine and l-Carnitine have been shown to be beneficial during cancer cachexia. Based on the above findings, we propose that a combination of Myostatin antagonist and Omega-3 fatty acids or Leucine or l-Carnitine may have potential to improve muscle mass during cancer cachexia.
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Publication Name
PharmaNutrition
Volume
2
ISBN/ISSN
2213-4344
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Issue
3
Pages Count
3
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Publisher
Elsevier
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EISSN
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DOI
10.1016/j.phanu.2013.07.002