Attenuation of skeletal muscle atrophy in cancer cachexia by d-myo-inositol 1,2,6-triphosphate

Russell, Steve T., Siren, P.M.A., Siren, M.J. and Tisdale, Michael J. (2009). Attenuation of skeletal muscle atrophy in cancer cachexia by d-myo-inositol 1,2,6-triphosphate. Cancer Chemotherapy and Pharmacology, 64 (3), pp. 517-527.

Abstract

PURPOSE: To determine the effectiveness of the polyanionic, metal binding agent D-myo-inositol-1,2,6-triphosphate (alpha trinositol, AT), and its hexanoyl ester (HAT), in tissue wasting in cancer cachexia. METHODS: The anti-cachexic effect was evaluated in the MAC16 tumour model. RESULTS: Both AT and HAT attenuated the loss of body weight through an increase in the nonfat carcass mass due to an increase in protein synthesis and a decrease in protein degradation in skeletal muscle. The decrease in protein degradation was associated with a decrease in activity of the ubiquitin-proteasome proteolytic pathway and caspase-3 and -8. Protein synthesis was increased due to attenuation of the elevated autophosphorylation of double-stranded RNA-dependent protein kinase, and of eukaryotic initiation factor 2alpha together with hyperphosphorylation of eIF4E-binding protein 1 and decreased phosphorylation of eukaryotic elongation factor 2. In vitro, AT completely attenuated the protein degradation in murine myotubes induced by both proteolysis-inducing factor and angiotensin II. CONCLUSION: These results show that AT is a novel therapeutic agent with the potential to alleviate muscle wasting in cancer patients.

Publication DOI: https://doi.org/10.1007/s00280-008-0899-z
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Additional Information: The original publication is available at www.springerlink.com
Uncontrolled Keywords: muscle atrophy,alpha trinositol,protein kinase R,PKR,eukaryotic initiation factors,eukaryotic elongation factors,Cancer Research,Oncology,Pharmacology (medical),Pharmacology,Toxicology
Full Text Link: http://www.spri ... 2185ux0413qh37/
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2009-07
Authors: Russell, Steve T.
Siren, P.M.A.
Siren, M.J.
Tisdale, Michael J.

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