Cancer is the second leading cause of death worldwide, with 9.6 million people estimated to have died of cancer in 2018. Excess body fat deposition is a risk factor for many types of cancer. Men and women exhibit differences in body fat distribution and energy homeostasis regulation. This systematic review aimed to understand why sex disparities in obesity are associated with sex differences in the incidence of gastrointestinal cancers. Cancers of the esophagus, liver, and colon are representative gastrointestinal cancers, and obesity is a convincing risk factor for their development. Numerous epidemiological studies have found sex differences in the incidence of esophageal, liver, and colorectal cancers. We suggest that these sexual disparities are partly explained by the availability of estrogens and other genetic factors regulating inflammation, cell growth, and apoptosis. Sex differences in gut microbiota composition may contribute to differences in the incidence and phenotype of colorectal cancer. To establish successful practices in personalized nutrition and medicine, one should be aware of the sex differences in the pathophysiology and associated mechanisms of cancer development.

Skeletal muscle atrophy is one of the major symptoms of cancer cachexia. Garlic (Allium sativum), one of the world’s most commonly used and versatile herbs, has been employed for the prevention and treatment of diverse diseases for centuries. In the present study, we found that ajoene, a sulfur compound found in crushed garlic, exhibits protective effects against muscle atrophy. Using CT26 tumor-bearing BALB/c mice, we demonstrate in vivo that ajoene extract alleviated muscle degradation by decreasing not only myokines secretion but also janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and SMADs/forkhead box (FoxO) signaling pathways, thereby suppressing muscle-specific E3 ligases. In mouse skeletal myoblasts, Z-ajoene enhanced myogenesis as evidenced by increased expression of myogenic markers via p38 mitogen-activated protein kinase (MAPK) activation. In mature myotubes, Z-ajoene protected against muscle protein degradation induced by conditioned media from CT26 colon carcinoma cells, by suppressing expression of muscle specific E3 ligases and nuclear transcription factor kappa B (NF-κB) phosphorylation which contribute to muscle atrophy. Moreover, Z-ajoene treatment improved myofiber formation via stimulation of muscle protein synthesis. These findings suggest that ajoene extract and Z-ajoene can attenuate skeletal muscle atrophy induced by cancer cachexia through suppressing inflammatory responses and the muscle wasting as well as by promoting muscle protein synthesis.

Objectives Skeletal muscle atrophy is caused by various diseases and conditions including aging, cancer, and cancer treatments. Chemotherapy-induced muscle atrophy leads to decrease quality of life and increase morbidity and mortality. Recent evidence suggests oxidative stress is a cause and/or consequence of mitochondrial dysfunction, which is strongly associated with muscle atrophy. Given Camellia japonica roots extract (CJT) has antioxidant property, we investigated whether CJT would ameliorate myoblast differentiation and chemotherapy-induced muscle atrophy in vitro and in vivo to provide evidence for candidates to prevent and treat muscle atrophy. Methods C2C12 myoblasts were differentiated in the presence of CJT (0.1, 1, 10, and 100 ng/mL) and cells were collected to perform myosin heavy chain (MHC) immunostaining and qRT-PCR for the measurement of markers related with myogenesis and mitochondrial function. Wild type AB * zebrafish (Danio rerio) embryos were treated with FOLFIRI (5-FU, LV, and CPT-11) and CJT, and immunostained to detect slow and fast types of muscle. The Tg(Xla.Eef1a1: mlsEGFP) zebrafish line expressing mitochondria-targeted green fluorescent protein (mito-GFP) was used to monitor mitochondrial morphology. Results CJT increased the formation of MHC-positive multinucleated myotubes (≥5 nuclei) in a dose-dependent manner, while it decreased the number of mononuclear myotubes. CJT significantly enhanced the expression of myogenic differentiation markers including Myod (early stage), Myog (mid stage), and MHC isoforms (late stage) including Myh 1, Myh 2, Myh 4, and Myh7. Mitochondrial biogenesis markers such as SDHA (Complex Ⅱ) and COX1 (Complex IV) were significantly increased at 100 ng/mL of CJT than control. CJT tended to increase the expression of MFN2 and NRF1 involved in mitochondrial fusion and biogenesis, respectively. In addition, CJT alleviated FOLFIRI-induced muscle atrophy both in slow and fast muscle fibers in zebrafish embryos. Similarly, CJT improved FOLFIRI-induced mitochondrial dysfunction in a dose-dependent manner. Conclusions Our data indicates that CJT promotes myogenesis and alleviates muscle atrophy in association with mitochondrial function, suggesting CJT has potential as a nutritional supplement for the prevention and treatment of muscle atrophy. Funding Sources NRF (2020R1C1C1007553 to S-EK)

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