| Budget Amount *help |
¥65,130,000 (Direct Cost: ¥50,100,000、Indirect Cost: ¥15,030,000)
Fiscal Year 2015: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2014: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2013: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2012: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Outline of Final Research Achievements |
In the course of screening for a new AR antagonist, we isolated novel compounds, antarlides A-E, from the Streptomyces sp. BB47. In addition, antarlide B inhibited the transcriptional activity of not only wild type AR but also mutant ARs, which are seen in patients with acquired resistance to clinically used AR antagonists.We next observed that xanthohumol (XN), a prenylated chalcone, modulates autophagy. By using XN-immobilized beads, valosin-containing protein (VCP) was identified as a XN-binding protein. These data indicated that XN inhibited the function of VCP, thereby allowing the impairment of autophagosome maturation. We also screened the compound that induced cell death selectively in tumor cell lines harboring β-catenin mutation from an in-house natural product library, and finally we isolated and found that nonactin. Furthermore, nonactin induced tumor regression only in β-catenin mutated HCT116 xenograft mice.
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