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Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium.

Wang H, Li TL, Hsia S, Su IL, Chan YL, Wu CJ - Oncotarget (2015)

Bottom Line: In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation.In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy.The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.

ABSTRACT
Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

No MeSH data available.


Related in: MedlinePlus

Final body weight gain for line-1, docetaxel or combined treatment miceAfter sacrifice we scaled mice body weight into two groups according to the body weight loss percentage. The body weight loss >10% or <10% is designated as severe cachexia or moderate cachexia. (A and C) On day 35 and 42 after tumor implantation, we harvest tumor and subtract tumor weight from final body weight to calculate the percentage of body weight loss for line-1 (A), docetaxel (B), or combined chemotherapy (C) treatment mice, respectively. Data show mean ± SD, n = 5–10 mice/group, each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.
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Figure 1: Final body weight gain for line-1, docetaxel or combined treatment miceAfter sacrifice we scaled mice body weight into two groups according to the body weight loss percentage. The body weight loss >10% or <10% is designated as severe cachexia or moderate cachexia. (A and C) On day 35 and 42 after tumor implantation, we harvest tumor and subtract tumor weight from final body weight to calculate the percentage of body weight loss for line-1 (A), docetaxel (B), or combined chemotherapy (C) treatment mice, respectively. Data show mean ± SD, n = 5–10 mice/group, each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.

Mentions: In animal study, mice were divided into two groups, severe and moderate cachexia as described previously (protocol #1) [18]. The former is redefined as >10% body weight loss for simplicity. In Table 1A, the carcass weight of the tumor-bearing mice (TB) is lighter than that of control mice [26]. In terms of tumor weight, the severe cachectic mice are 2-fold heavier than the moderate (Table 1A). The body weight, however, gained about 10.2% in normal mice, as opposed to the body weight losses, 5.6% and 19.1%, in moderately and severely cachectic mice, respectively (Figure 1A). The body weight loss can thereby index the severity of the tumor-induced cachexia. The loss of muscle/fat (e.g., epididymal fat) accounts for the major weight loss (Table 1A). Though anorexia usually comes with cancer cachexia, food intake made no difference between the experiment and control groups (Table 1B). Given that inflammation and hypoalbuminemia are two diagnostic indices for cachexia [27], the level of albumin in the severe cachectic mice was not surprised significantly lower (p < 0.05, TModerate vs. TSevere) than that in the moderate (Table 2A). Serum TNF-α and IL-6 in the severe cancer group were higher than those in control, whereas serum IL-1β leveled off in all groups (Table 2A).


Skeletal muscle atrophy is attenuated in tumor-bearing mice under chemotherapy by treatment with fish oil and selenium.

Wang H, Li TL, Hsia S, Su IL, Chan YL, Wu CJ - Oncotarget (2015)

Final body weight gain for line-1, docetaxel or combined treatment miceAfter sacrifice we scaled mice body weight into two groups according to the body weight loss percentage. The body weight loss >10% or <10% is designated as severe cachexia or moderate cachexia. (A and C) On day 35 and 42 after tumor implantation, we harvest tumor and subtract tumor weight from final body weight to calculate the percentage of body weight loss for line-1 (A), docetaxel (B), or combined chemotherapy (C) treatment mice, respectively. Data show mean ± SD, n = 5–10 mice/group, each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480714&req=5

Figure 1: Final body weight gain for line-1, docetaxel or combined treatment miceAfter sacrifice we scaled mice body weight into two groups according to the body weight loss percentage. The body weight loss >10% or <10% is designated as severe cachexia or moderate cachexia. (A and C) On day 35 and 42 after tumor implantation, we harvest tumor and subtract tumor weight from final body weight to calculate the percentage of body weight loss for line-1 (A), docetaxel (B), or combined chemotherapy (C) treatment mice, respectively. Data show mean ± SD, n = 5–10 mice/group, each value is an average of three independent experiments. *p < 0.05, **p < 0.01, and ***p < 0.001 denote levels of significant differences between groups.
Mentions: In animal study, mice were divided into two groups, severe and moderate cachexia as described previously (protocol #1) [18]. The former is redefined as >10% body weight loss for simplicity. In Table 1A, the carcass weight of the tumor-bearing mice (TB) is lighter than that of control mice [26]. In terms of tumor weight, the severe cachectic mice are 2-fold heavier than the moderate (Table 1A). The body weight, however, gained about 10.2% in normal mice, as opposed to the body weight losses, 5.6% and 19.1%, in moderately and severely cachectic mice, respectively (Figure 1A). The body weight loss can thereby index the severity of the tumor-induced cachexia. The loss of muscle/fat (e.g., epididymal fat) accounts for the major weight loss (Table 1A). Though anorexia usually comes with cancer cachexia, food intake made no difference between the experiment and control groups (Table 1B). Given that inflammation and hypoalbuminemia are two diagnostic indices for cachexia [27], the level of albumin in the severe cachectic mice was not surprised significantly lower (p < 0.05, TModerate vs. TSevere) than that in the moderate (Table 2A). Serum TNF-α and IL-6 in the severe cancer group were higher than those in control, whereas serum IL-1β leveled off in all groups (Table 2A).

Bottom Line: In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation.In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy.The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.

ABSTRACT
Chemotherapy can cause cachexia, which is manifested by weight loss, inflammation and muscle atrophy. However, the mechanisms of tumor and chemotherapy on skeletal muscle proteolysis, remained unclear. In this report, we demonstrated that tumor-induced myostatin in turn induced TNF-α, thus activating calcium-dependent and proteasomal protein degradation. Chemotherapy activated myostatin-mediated proteolysis and muscle atrophy by elevating IL-6. In tumor-bearing mice under chemotherapy, supplementation with fish oil and selenium prevented a rise in IL-6, TNF-α and myostatin and muscle atrophy. The findings presented here allow us to better understand the molecular basis of cancer cachexia and potentiate nutrition supplementation in future cancer chemotherapy.

No MeSH data available.


Related in: MedlinePlus