Elucidation of bioavailability and anticancer property of momilactones and natural anticancer compounds isolated from rice

阐明从大米中分离的莫米内酯和天然抗癌化合物的生物利用度和抗癌特性

• 批准号: 21K14818
• 负责人: NGUYEN VANQUAN
• 金额: $ 2.91万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K14818/
• 关键词: momilactones; anti-blood cancer; bioaccessibility; in vitro digestion; cytotoxicity; blood cancer; momilactone; anticancer; rice; phytocompounds; bioavailability

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.

阐明了Momilactones A（MA）和B（MB）针对包括急性前临床细胞白血病和多发性骨髓瘤在内的血液癌细胞系的细胞毒性机制。根据MTT结果，其中MB和混合物mAb（1：1，w/w）对HL-60和U266的细胞生存能力有很大的抑制作用，IC50范围为4.49至5.59 um。此外，通过对凋亡诱导的因子（P-38，Bcl-2和Caspase-3）和G2期（P-38，CDK1和Cyclin B1）的相关蛋白质（P-38，BCL-2和CASPASE-3）和细胞周期停滞，MB和MAB通过相关蛋白与凋亡诱导的因子（P-38，BCL-2和CASPASE-3）的法规抑制HL-60细胞。同时，这些化合物通过改变P-38，BCL-2和caspase-3信号通路来增强U266的凋亡。值得注意的是，Momilactones对非癌细胞系（MET-5A）表现出较小的影响，这意味着它们被保证是为开发新型抗APL和抗MM药物的候选人。结果发表在癌症上。此外，研究了体外消化对抗血脂癌和MA和MB的生物可获得性的影响。结果表明，MB和MAB的细胞毒性活性得到了显着改善。此外，MOMILACTONES的生物恢复性显着降低（从28.44％到75.14％），这与它们在消化下的细胞毒性降低密切相关。这些发现是在日本生物科学，生物技术和农业化学学会2023年会上（日本农业化学学会2023会议）的2023年会议上提出的，在线会议，2023年3月。

项目成果

Effects of in vitro digestion on momilactones and their anti-blood cancer activity

体外消化对莫米内酯及其抗血癌活性的影响

• 发表时间: 2023
• 作者: Anh La Hoang;Lam Vu Quang;Takami Akiyoshi;Khanh Tran Dang;Quan Nguyen Van;Xuan Tran Dang;La Hoang Anh
• 通讯作者: La Hoang Anh

Anti-blood cancer property of momilactones A and B from rice husks

稻壳中的莫米内酯 A 和 B 的抗血癌特性

• 发表时间: 2021
• 作者: Anh La Hoang;Lam Vu Quang;Takami Akiyoshi;Khanh Tran Dang;Quan Nguyen Van;Xuan Tran Dang;La Hoang Anh;La Hoang Anh
• 通讯作者: La Hoang Anh