Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expression.
Cancer cachexia syndrome contributes to wasting and weight loss leading to inefficacy of anticancer therapy. In this study, the anticatabolic agent beta-hydroxy-beta-methylbutyrate (HMB) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aiming to determine if tumor burden could be reduced. Male Wistar rats were randomly assigned to nontumor and tumor-bearing groups and fed regular chow or regular chow plus HMB supplemented (76 mg/kg body weight). Beta-hydroxy-beta-methylbutyrate supplementation induced a lower tumor weight and tumor cell proliferation ex vivo, totally prevented glycemia reduction, as well as blunted the increase in the serum lactate concentrations and also preserved glycogen stores in tumor-bearing rats. Reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-kappaB inhibitor-alpha content by more than 100%. In contrast, nuclear factor-kappaB p65 subunit content was suppressed by 17% with HMB supplementation. In conclusion, HMB supplementation, at a similar dose used in humans to increase muscle mass, caused antitumor and anticachectic effects, with tumor-cell nuclear factor-kappaB pathway participation, which might be a potential nutritional strategy in cancer therapy.
Nunes
Everson Araújo
EA
Department of Physiology, Biological Science Building, Federal University of Paraná, 81531-980 Curitiba-PR, Brazil. eanunes@ufpr.br
Kuczera
Diogo
D
Brito
Gleisson Alisson Pereira
GA
Bonatto
Sandro J R
SJ
Yamazaki
Ricardo Key
RK
Tanhoffer
Ricardo Antonio
RA
Mund
Rogéria Campus
RC
Kryczyk
Marcelo
M
Fernandes
Luiz Claudio
LC
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control*; D002279:Carcinoma 256, Walker / Q000737:chemistry / Q000150:complications / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006003:Glycogen / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D016328:NF-kappa B / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D014631:Valerates / Q000008:administration & dosage*
D016328:NF-kappa B; D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D006003:Glycogen