| 配分額 *注記 |
4,550千円 (直接経費: 3,500千円、間接経費: 1,050千円)
2024年度: 910千円 (直接経費: 700千円、間接経費: 210千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2021年度: 910千円 (直接経費: 700千円、間接経費: 210千円)
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| 研究開始時の研究の概要 |
This project will be conducted from April, 2021 to March, 2025 in order to elucidate the effect of MA and MB and natural anticancer compounds derived from rice on various cancers; and to discover the optimal ratios of the natural compounds that can be efficiently applied in therapeutics.
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| 研究実績の概要 |
The cytotoxic mechanism of momilactones A (MA) and B (MB) against blood cancer cell lines including acute promyelocytic leukemia and multiple myeloma were clarified. Of which, According to MTT results, MB and the mixture MAB (1:1, w/w) show a substantial inhibition on the cell viability of HL-60 and U266, with IC50 ranging from 4.49 to 5.59 uM. Besides, MB and MAB at 5 uM inhibit HL-60 cells through the regulations of relevant proteins to apoptosis-inducing factors (p-38, BCL-2, and caspase-3) and cell cycle arrest at G2 phase (p-38, CDK1, and cyclin B1). Meanwhile, these compounds enhance U266 apoptosis by altering p-38, BCL-2, and caspase-3 signaling pathways. Significantly, momilactones exhibit a minor effect on a non-cancerous cell line (MeT-5A), implying that they are promising candidates for developing novel anti-APL and anti-MM medicines. The results were published on Cancers. In addition, the effects of in vitro digestion on anti-blood cancer and bioaccessibility of MA and MB were investigated. Results reveal that the cytotoxic activities of MB and MAB were dramatically decreased. In addtition, the bioaccessibility of momilactones was significantly reduced (from 28.44% to 75.14%) which was strongly correlated with their decreased cytotoxicity under digestion. The findings were presented at the 2023 Annual Meeting of the Japan Society for Bioscience, Biotechnology, and Agrochemistry (日本農芸化学会2023年度大会), Online meeting, March 2023.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
- Thanks to the enthusiastic support and collaboration with the Hematology Lab led by Prof. Dr. Takami Akiyoshi at Aichi Medical University, we could successfully clarify cytototic mechanisms of momilactone on blood cancer cells.
- With a good preparation of in vitro digestion protocol, we could screen the effect of in vitro digestion model on the accessibility and cytotoxicity of momilactones.
- The isolation and purification of other new active compounds took longer time than we expected due to the operation of column chromatogram and purification process.
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