Suppression of cancer metastases by hop-derived prenylflavonoids and drug discovery research

Research Project

Project/Area Number	15K14411
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Tumor therapeutics
Research Institution	Tokyo Women's Medical University
Principal Investigator	Morichika Takita 東京女子医科大学, 医学部, 助教 (80533455)
Research Collaborator	MARU Yoshiro 東京女子医科大学, 医学部, 教授 (00251447)
Project Period (FY)	2015-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords	プレニル化フラボノイド / 抗腫瘍活性 / アポトーシス / カスパーゼ-3 / 破骨細胞 / 骨破壊 / 肺転移 / 骨転移 / がん細胞増殖抑制 / 破骨細胞形成抑制 / キサントフモール
Outline of Final Research Achievements	Hop-derived prenylflavonoids, exemplified as xanthohumol (Xh), have various biological activities. However, effectiveness of Xh for systemic cancer metastases and osteolysis accompanied by bone metastasis is not clear. In this study, anti-metastatic and anti-osteolytic potentials of Xh have been investigated. In vitro, Xh promoted apoptosis via caspase-3 activation and inhibited cell growth in metastatic cancer cells. Xh inhibited osteoclast formation induced by the cell-to-cell contact between metastatic cancer cells and host osteoblasts, and attenuated osteolysis induced by co-culture with metastatic cancer cells in the mouse calvarial organ culture system. Furthermore, Xh also attenuated both lung and bone metastases in the mouse systemic cancer metastases model which was made by intravenous injection of the metastatic B16 melanoma cell line in vivo.