Molecular targets of cancer cachexia: opportunities for pharmanutritional approaches

Sharma, Mridula, Kambadur, Ravi, Sriram, Sandhya, Lokireddy, Sudarsanareddy, and McFarlane, Craig (2014) Molecular targets of cancer cachexia: opportunities for pharmanutritional approaches. PharmaNutrition, 2 (3). pp. 126-128.

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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.

Item ID: 52354
Item Type: Article (Short Note)
ISSN: 2213-4344
Keywords: myostatin; cancer cachexia; ROS
Funders: Biomedical Research Council, Singapore (BMRC), National Research Foundation, Singapore (NRFS)
Date Deposited: 13 Apr 2018 04:34
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy) @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111207 Molecular Targets @ 40%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 20%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 33%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 33%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 34%
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