title: β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice.
abstract: We reported previously that high-fat diet (HFD) feeding stimulated solid tumor growth and lymph node (LN) metastasis in C57BL/6N mice injected with B16F10 melanoma cells. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils and has been shown to exert anti-inflammatory activities. To examine whether BCP inhibits HFD-induced melanoma progression, 4-weeks old, male C57BL/6N mice were fed a control diet (CD, 10 kcal% fat) or HFD (60 kcal% fat + 0, 0.15 or 0.3% BCP) for the entire experimental period. After 16 weeks of feeding, B16F10s were subcutaneously injected into mice. Three weeks later, tumors were resected, and mice were killed 2 weeks post-resection. Although HFD feeding increased body weight gain, fasting blood glucose levels, solid tumor growth, LN metastasis, tumor cell proliferation, angiogenesis and lymphangiogenesis, it decreased apoptotic cells, all of which were suppressed by dietary BCP. HFD feeding increased the number of lipid vacuoles and F4/80+ macrophage (MΦ) and macrophage mannose receptor (MMR)+ M2-MΦs in tumor tissues and adipose tissues surrounding the LN, which was suppressed by BCP. HFD feeding increased the levels of CCL19 and CCL21 in the LN and the expression of CCR7 in the tumor; these changes were blocked by dietary BCP. In vitro culture results revealed that BCP inhibited lipid accumulation in 3T3-L1 preadipocytes; monocyte migration and monocyte chemoattractant protein-1 secretion by B16F10s, adipocytes and M2-MΦs; angiogenesis and lymphangiogenesis. The suppression of adipocyte and M2-cell accumulation and the inhibition of CCL19/21-CCR7 axis may be a part of mechanisms for the BCP suppression of HFD-stimulated melanoma progression.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, 1 Hallymdaehak-gil, Chuncheon 200-702, Korea.
authors.forename: Jae In
authors.initials: JI
authors.lastname: Jung
authors.affiliation: Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, Hallym University, 1 Hallymdaehak-gil, Chuncheon 200-702, Korea.
authors.forename: Gyoo Taik
authors.initials: GT
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Nutrition, Hallym University, 1 Hallymdaehak-gil, Chuncheon 200-702, Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Statistics and Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Korea, Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Korea.
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Statistics and Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Korea.
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
authors.affiliation: Center for Food and Nutritional Genomics Research and Department of Food Science and Nutrition, Kyungpook National University, Daegu 702-701, Korea.
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Food Science and Technology, Chung-Ang University, An-Sung 456-756, Korea.
authors.forename: Hyang Sook
authors.initials: HS
authors.lastname: Chun
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Korea.
authors.forename: Seung-Hae
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, Korea.
authors.forename: Song
authors.initials: S
authors.lastname: Her
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea and Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Food Science and Nutrition, Hallym University, 1 Hallymdaehak-gil, Chuncheon 200-702, Korea, Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Korea jyoon@hallym.ac.kr.
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054415:Chemokine CCL19 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D054421:Chemokine CCL21 / Q000037:antagonists & inhibitors / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats; D037181:Lectins, C-Type / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008264:Macrophages / Q000166:cytology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000517:prevention & control; D009765:Obesity / Q000473:pathology; D000081223:Polycyclic Sesquiterpenes; D011897:Random Allocation; D054400:Receptors, CCR7 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D050151:Subcutaneous Fat / Q000166:cytology / Q000473:pathology; D014617:Vacuoles / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C515461:Ccl19 protein, mouse; C491768:Ccl2 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054421:Chemokine CCL21; D004041:Dietary Fats; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D000081223:Polycyclic Sesquiterpenes; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D012717:Sesquiterpenes; C024714:caryophyllene