2022 Fiscal Year Research-status Report
Elucidation of bioavailability and anticancer property of momilactones and natural anticancer compounds isolated from rice
| Project/Area Number |
21K14818
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| Research Institution | Hiroshima University |
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Principal Investigator |
NGUYEN VANQUAN 広島大学, 先進理工系科学研究科(国), 助教 (90883033)
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| Project Period (FY) |
2021-04-01 – 2025-03-31
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| Keywords | momilactones / anti-blood cancer / bioaccessibility / in vitro digestion |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
- 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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| Strategy for Future Research Activity |
- To complete purification of other bioactive compounds and checking their anticancer properties in a combination with momilactones and other synthetically commercial drugs.
- To evaluate and confirm the anticancer properties of the combinations of momilactones and natural compounds from rice based on natural killer cell assays.
- To investigate the contents of momilactones and other anticancer compounds from fermented rice products, in order to find out a potential method for improving accessibility of momilactones.
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