title: Benzyl isothiocyanate suppresses high-fat diet-stimulated mammary tumor progression via the alteration of tumor microenvironments in obesity-resistant BALB/c mice.
abstract: We previously reported that a high-fat diet (HFD) and M2-macrophages induce changes in tumor microenvironments and stimulate tumor growth and metastasis of 4T1 mammary cancer cells in BALB/c mice. In this study, we attempted to determine whether benzyl isothiocyanate (BITC) inhibits HFD-induced changes in tumor progression and in tumor microenvironments. Four groups of female BALB/c mice (4-week-old) were fed on a control diet (CD, 10 kcal% fat) and HFD (60 kcal% fat) containing BITC (0, 25, or 100 mg/kg diet) for 20 weeks. Following 16 weeks of feeding, 4T1 cells (5×10(4) cells) were injected into the mammary fat pads, and animals were killed 30 d after the injection. HFD feeding increased solid tumor growth and the number of tumor nodules in the lung and liver, as compared to the CD group, and these increases were inhibited by BITC supplementation. The number of lipid vacuoles, CD45+ leukocytes and CD206+ M2-macrophages, expression of Ki67, levels of cytokines/chemokines, including macrophage-colony stimulating factor (M-CSF) and monocyte chemoattractant protein-1, and mRNA levels of F4/80, CD86, Ym1, CD163, CCR2, and M-CSF receptor were increased in the tumor tissues of HFD-fed mice, and these increases were inhibited by BITC supplementation. In vitro culture results demonstrated that BITC inhibited macrophage migration as well as lipid droplet accumulation in 3T3-L1 cells. These results suggest that suppression of lipid accumulation and macrophage infiltration in tumor tissues may be one of the mechanisms by which BITC suppresses tumor progression in HFD-fed mice.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon, Korea.
authors.forename: Minhee
authors.initials: M
authors.lastname: Kim
authors.forename: Han Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Gyoo Taik
authors.initials: GT
authors.lastname: Kwon
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
authors.forename: Seung-Hae
authors.initials: SH
authors.lastname: Kwon
authors.forename: Song
authors.initials: S
authors.lastname: Her
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Kim
authors.forename: Yun
authors.initials: Y
authors.lastname: Kee
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000494:pharmacology; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary*; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009765:Obesity / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D004041:Dietary Fats; D017879:Isothiocyanates; C031403:benzyl isothiocyanate
keywords: BITC; cytokines; macrophages; mammary tumor metastasis