title: Onionin A inhibits ovarian cancer progression by suppressing cancer cell proliferation and the protumour function of macrophages.
abstract: It is well known that tumour-associated macrophages (TAMs) play an important role in tumour development by modulating the tumour microenvironment, and targeting of protumour activation or the M2 polarization of TAMs is expected to be an effective therapy for cancer patients. We previously demonstrated that onionin A (ONA), a natural low molecular weight compound isolated from onions, has an inhibitory effect on M2 macrophage polarization. In the present study, we investigated whether ONA had a therapeutic anti-ovarian cancer effect using in vitro and in vivo studies. We found that ONA reduced the extent of ovarian cancer cell proliferation induced by co-culture with human macrophages. In addition, we also found that ONA directly suppressed cancer cell proliferation. A combinatorial effect with ONA and anti-cancer drugs was also observed. The activation of signal transducer and activator of transcription 3 (STAT3), which is involved in cell proliferation and chemo-resistance, was significantly abrogated by ONA in ovarian cancer cells. Furthermore, the administration of ONA suppressed cancer progression and prolonged the survival time in a murine ovarian cancer model under single and combined treatment conditions. Thus, ONA is considered useful for the additional treatment of patients with ovarian cancer owing to its suppression of the protumour activation of TAMs and direct cytotoxicity against cancer cells.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.|Obsterics and Gynecology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Tsuboki
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Hasita
authors.initials: H
authors.lastname: Horlad
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shiraishi
authors.affiliation: Department of Natural Medicine, Faculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nohara
authors.affiliation: Obsterics and Gynecology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Tayama
authors.affiliation: Obsterics and Gynecology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Motohara
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Natural Medicine, Faculty of Pharmaceutical Sciences, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto 860-0082, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Obsterics and Gynecology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Takaishi
authors.affiliation: Department of Mother-Child Nursing, Faculty of Life Sciences, Kumamoto University, Kuhonji 4-24-1, Chuo-ku, Kumamoto 862-0976, Kumamoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Tashiro
authors.affiliation: Priority Organization for Innovation and Excellence, Kumamoto University, Kurokami 2-39-1, Chuo-ku, Kumamoto 860-8555, Kumamoto, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yonemoto
authors.affiliation: Obsterics and Gynecology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Katabuchi
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Kumamoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000628:therapy*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013454:Sulfoxides / Q000494:pharmacology*; D015996:Survival Rate; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013454:Sulfoxides; D013876:Thiophenes; C551608:onionin A