title: 6-shogaol, an active constituent of dietary ginger, impairs cancer development and lung metastasis by inhibiting the secretion of CC-chemokine ligand 2 (CCL2) in tumor-associated dendritic cells.
abstract: This study has two novel findings: it is not only the first to demonstrate that tumor-associated dendritic cells (TADCs) facilitate lung and breast cancer metastasis in vitro and in vivo by secreting inflammatory mediator CC-chemokine ligand 2 (CCL2), but it is also the first to reveal that 6-shogaol can decrease cancer development and progression by inhibiting the production of TADC-derived CCL2. Human lung cancer A549 and breast cancer MDA-MB-231 cells increase TADCs to express high levels of CCL2, which increase cancer stem cell features, migration, and invasion, as well as immunosuppressive tumor-associated macrophage infiltration. 6-Shogaol decreases cancer-induced up-regulation of CCL2 in TADCs, preventing the enhancing effects of TADCs on tumorigenesis and metastatic properties in A549 and MDA-MB-231 cells. A549 and MDA-MB-231 cells enhance CCL2 expression by increasing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), and the activation of STAT3 induced by A549 and MDA-MB-231 is completely inhibited by 6-shogaol. 6-Shogaol also decreases the metastasis of lung and breast cancers in mice. 6-Shogaol exerts significant anticancer effects on lung and breast cells in vitro and in vivo by targeting the CCL2 secreted by TADCs. Thus, 6-shogaol may have the potential of being an efficacious immunotherapeutic agent for cancers.
authors.affiliation: Graduate Institute of Medicine, ‡School of Medicine, and ⊥Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung 807, Taiwan.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Hsu
authors.forename: Jen-Yu
authors.initials: JY
authors.lastname: Hung
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Tsai
authors.forename: Eing-Mei
authors.initials: EM
authors.lastname: Tsai
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; D002396:Catechols; D018932:Chemokine CCL2; C040115:shogaol
keywords: 6-shogaol; CCL2; breast cancer; lung cancer; metastasis