title: Lunasin Attenuates Obesity-Associated Metastasis of 4T1 Breast Cancer Cell through Anti-Inflammatory Property.
abstract: Obesity prevalence is increasing worldwide and is accompanied by low-grade inflammation with macrophage infiltration, which is linked with a poorer breast cancer prognosis. Lunasin is a natural seed peptide with chemopreventive properties and multiple bioactivities. This is the first study to explore the chemopreventive effects of lunasin in the obesity-related breast cancer condition using 4T1 breast cancer cells, 3T3-L1 adipocytes, and conditioned media. An obesity-related environment, such as leptin-treatment or adipocyte-conditioned medium (Ad-CM), promoted 4T1 cell proliferation and metastasis. Lunasin treatment inhibited metastasis of breast cancer cells, partially through modestly inhibiting production of the angiogenesis-mediator vascular endothelial growth factor (VEGF) and significantly by inhibiting secretion in the Ad-CM condition. Subsequently, two adipocytes inflammation models, 3T3-L1 adipocytes were stimulated by tumor necrosis factor (TNF)-α, and RAW 264.7 cell-conditioned medium (RAW-CM) was used to mimic the obese microenvironment. Lunasin significantly inhibited interleukin (IL)-6 and macrophage chemoattractant protein (MCP)-1 secretion by TNF-α stimulation, and MCP-1 secretion in the RAW-CM model. This study highlights that lunasin suppressed 3T3-L1 adipocyte inflammation and inhibited 4T1 breast cancer cell migration. Interestingly, lunasin exerted more effective anti-metastasis activity in the obesity-related condition models, indicating that it possesses anti-inflammatory properties and blocks adipocyte-cancer cell cross-talk.
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 10610, Taiwan. hsieh@ntnu.edu.tw.
authors.forename: Chia-Chien
authors.initials: CC
authors.lastname: Hsieh
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 10610, Taiwan. joyce.walawala@gmail.com.
authors.forename: Chih-Hsuan
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 10610, Taiwan. z83526@hotmail.com.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Huang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D015674:Mammary Neoplasms, Animal / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009765:Obesity / Q000150:complications* / Q000188:drug therapy; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D000067996:RAW 264.7 Cells; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D020738:Leptin; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A
keywords: adipocyte; breast cancer; inflammation; lunasin; metastasis