Parthenolide from Parthenium integrifolium reduces tumor burden and alleviate cachexia symptoms in the murine CT-26 model of colorectal carcinoma

Abstract

Excessive elaboration of proinflammatory cytokines are involved in cachexia-related hypercatabolism. Parthenolide, as a potential anti-inflammatory active agent, could effectively inhibit nuclear factor-kappa B, and has the potential for the treatment of cancer cachexia. In this study, the cancer cachexia model was established by subcutaneous transplantation CT26 tumor fragment. Parthenolide or placebo was intraperitoneally given daily from the next day. Parthenolide treatment could effectively preserve the body weight, improve the mass of gastrocnemius and tibialis anterior muscles, and alleviate tumor burden. Sizes of muscle fibers and myosin heavy chain were also increasing. The serum proinflammatory cytokine TNF-α level was lower than placebo treatment mice measure by ELISA. To investigate the possible mechanism, MuRF1 and Fbx32 was subjected to Western blot analysis and expression of MURF1 was inhibited in gastrocnemius muscle. Collectively, parthenolide treatment could effectively alleviate tumor burden of cachexia, preserve the body weight and improve skeletal muscle characteristics.

Keywords: Cancer cachexia; Parthenium integrifolium; Parthenolide; Skeletal muscle; Tumor burden.