title: Bax/Bcl-2 protein expression ratio and leukocyte function are related to reduction of Walker-256 tumor growth after β-hydroxy-β-methylbutyrate (HMB) administration in Wistar rats.
abstract: This study investigated the mechanisms by which β-hydroxy-β-methylbutyrate (HMB) administration in rats reduces Walker-256 tumor growth. Male Wistar rats were supplemented with HMB (76 mg/kg/day) (HW), or a placebo (W), during 8 wk by gavage. At the 6th wk, rats were inoculated with a suspension of Walker 256 tumor cells (3 × 10(7)/mL). Fifteen days after inoculation, the HW group showed higher glycemia (109.4 ± 5.53 vs. 89.87 ± 7.02 mg/dL, P < 0.05) and lower spleen (1.35 ± 0.05 vs. 1.65 ± 0.12 g, P < 0.05) and tumor weights (9.64 ± 1.07 vs. 13.55 ± 1.19 g, P < 0.05) compared to the W group. Tumor cells extracted from the HMB-treated rats displayed a 36.9% decrement in rates of proliferation ex vivo and a significant increase in the Bax/Bcl-2 protein expression ratio in comparison to those extracted from the placebo-treated rats (P < 0.05). Both phagocytic capacity and H(2)O(2) production rates were higher in polymorphnuclear cells that were obtained from the blood of the HW rats in comparison to those from the W rats (P < 0.05). Reduction of necrotic regions and an intense infiltration of leukocytes and activated granulocytes in HW were evident by transmission electron microscopy. Our findings suggest that HMB supplementation decreases tumor burden by modifying the inner environment of tumor cells and by interfering with blood leukocyte function.
authors.affiliation: Cell Biology Department, Biological Science Building, Federal University of Paraná, Curitiba-PR, Brazil.
authors.forename: Diogo
authors.initials: D
authors.lastname: Kuczera
authors.forename: Heloísa Helena
authors.initials: HH
authors.lastname: Paro de Oliveira
authors.forename: Fernando de Souza
authors.initials: Fde S
authors.lastname: Fonseca Guimarães
authors.forename: Carina
authors.initials: C
authors.lastname: de Lima
authors.forename: Luciana
authors.initials: L
authors.lastname: Alves
authors.forename: Andressa Franzói
authors.initials: AF
authors.lastname: Machado
authors.forename: Isabela
authors.initials: I
authors.lastname: Coelho
authors.forename: Adriana
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Lucélia
authors.initials: L
authors.lastname: Donatti
authors.forename: Katya
authors.initials: K
authors.lastname: Naliwaiko
authors.forename: Luiz Claudio
authors.initials: LC
authors.lastname: Fernandes
authors.forename: Everson Araújo
authors.initials: EA
authors.lastname: Nunes
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002279:Carcinoma 256, Walker / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D008297:Male; D046529:Microscopy, Electron, Transmission; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D014631:Valerates / Q000008:administration & dosage*; D051028:bcl-2-Associated X Protein / Q000032:analysis*
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014631:Valerates; D051028:bcl-2-Associated X Protein; C004961:beta-hydroxyisovaleric acid