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Onionin A, a sulfur‐containing compound isolated from onions, impairs tumor development and lung metastasis by inhibiting the protumoral and immunosuppressive functions of myeloid cells
Author(s) -
Fujiwara Yukio,
Horlad Hasita,
Shiraishi Daisuke,
Tsuboki Junko,
Kudo Rino,
Ikeda Tsuyoshi,
Nohara Toshihiro,
Takeya Motohiro,
Komohara Yoshihiro
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500995
Subject(s) - metastasis , cancer research , lung , myeloid , myeloid cells , chemistry , microbiology and biotechnology , immunology , medicine , biology , cancer
Scope Recent studies have demonstrated that myeloid lineage cells, such as macrophages and myeloid suppressor cells (MDSCs), are major components exhibiting protumoral functions in the setting of tumor progression. Tumor‐associated macrophages polarized to the protumoral M2 phenotype promote tumor proliferation and are considered to be a therapeutic target in patients with malignant tumors. Methods and results We identified a new candidate compound, called onionin A (ONA) isolated from onions, that inhibits macrophage polarization into the M2 phenotype, as well as the immunosuppressive activity of MDSCs and tumor proliferation, by suppressing signal transducer and activator of transcription‐3 (Stat3) activation. Furthermore, ONA administration was found to significantly suppress subcutaneous tumor development and lung metastasis in tumor‐bearing mice. ONA administration also inhibited Stat3 activation and increased the number of infiltrating lymphocytes in tumor tissues, and an ex vivo analysis showed that the immunosuppressive effect of MDSCs in tumor‐bearing mice is impaired by ONA. Moreover, ONA regulated tumor proliferation by inhibiting cell–cell interactions between macrophages and tumor cells, and ONA administration enhanced the antitumor effects of cisplatin in the tumor‐bearing mice. Conclusions These findings demonstrate that ONA may be a potential new tool for antitumor therapy and also for tumor prevention.