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: Junko Tsuboki, Yukio Fujiwara, Hasita Horlad, Daisuke Shiraishi, Toshihiro Nohara, Shingo Tayama, Takeshi Motohara, Yoichi Saito, Tsuyoshi Ikeda, Kiyomi Takaishi, Hironori Tashiro, Yukihiro Yonemoto, Hidetaka Katabuchi, Motohiro Takeya, Yoshihiro Komohara
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 29588 (07 12 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27404320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cytokines
• STAT3 Transcription Factor
• STAT3 protein, human
• Sulfoxides
• Thiophenes
• onionin A

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytokines (metabolism)
• Disease Progression
• Female
• Humans
• Macrophages (drug effects, metabolism)
• Mice, Inbred C57BL
• Ovarian Neoplasms (metabolism, therapy)
• STAT3 Transcription Factor (metabolism)
• Sulfoxides (pharmacology)
• Survival Rate
• Thiophenes (pharmacology)