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: Ya-Ling Hsu, Jen-Yu Hung, Ying-Ming Tsai, Eing-Mei Tsai, Ming-Shyan Huang, Ming-Feng Hou, Po-Lin Kuo
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 63 Issue 6 Pg. 1730-8 (Feb 18 2015) ISSN: 1520-5118 [Electronic] United States
• PMID: 25621970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Catechols
• Chemokine CCL2
• shogaol

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Breast Neoplasms (pathology)
• Catechols (administration & dosage, pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Chemokine CCL2 (antagonists & inhibitors, metabolism)
• Dendritic Cells (drug effects, metabolism)
• Diet
• Female
• Zingiber officinale (chemistry)
• Humans
• Immunotherapy
• Lung Neoplasms (pathology, secondary)
• Male
• Mice
• Neoplasm Invasiveness (pathology)
• Neoplasm Metastasis (prevention & control)
• Xenograft Model Antitumor Assays