Laricitrin ameliorates lung cancer-mediated dendritic cell suppression by inhibiting signal transducer and activator of transcription 3
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Wei-An Chang1,2, Jen-Yu Hung2,3, Shu-Fang Jian1, Yi-Shiuan Lin1, Cheng-Ying Wu1, Ya-Ling Hsu4, Po-Lin Kuo1,4,5
1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
2Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
3School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan
Po-Lin Kuo, email: firstname.lastname@example.org
Ya-Ling Hsu, email: email@example.com
Keywords: laricitrin, dendritic cell, lung cancer, IL-10, STAT3
Received: August 20, 2016 Accepted: October 24, 2016 Published: November 09, 2016
Natural polyphenolic compounds of grapes and their seeds are thought to be therapeutic adjuvants in a variety of diseases, including cancer prevention. This study was carried out to investigate the effect of grape phenolic compounds on the regulation of cancer-mediated immune suppression. Laricitrin exhibits the greatest potential to ameliorate the suppressive effects of lung cancer on dendritic cells’ (DCs’) differentiation, maturation and function. Human lung cancer A549 and CL1-5 cells change the phenotype of DCs that express to high levels of IL-10 and prime T cells towards an immune suppression type-2 response (Th2). Laricitrin treatment stimulated DC differentiation and maturation in the condition media of cancer cells, a finding supported by monocyte marker CD14’s disappearance and DC marker CD1a’s upregulation. Laricitrin decreases expression of IL-10 in cancer-conditioned DCs, and subsequently switches CD4+ T cell response from Th2 to Th1 in vitro and in vivo. Reversal of laricitrin on lung cancer-induced DCs’ paralysis was via inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Laricitrin also potentiated the anticancer activity of cisplatin in mouse models. Thus, laricitrin could be an efficacious immunoadjuvant and have a synergistic effect when combined with chemotherapy.
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