Dual-Targeting Antiproliferation Hybrids Derived from 1-Deoxynojirimycin and Kaempferol Induce MCF-7 Cell Apoptosis through the Mitochondria-Mediated Pathway
文献类型： 外文期刊
作者： Zhang, Ran 1 ; Zhang, Yueyue 1 ; Xin, Xiangdong 1 ; Huang, Gaiqun 1 ; Zhang, Ning 1 ; Zeng, Qinglei 1 ; Tang, Liumei 1 ;
作者机构： 1.Jiangsu Univ Sci & Technol, Sch Biotechnol, Zhenjiang 212100, Jiangsu, Peoples R China
2.Chinese Acad Agr Sci, Sericultural Res Inst, Zhenjiang 212100, Jiangsu, Peoples R China
3.Sichuan Acad Agr Sci, Sericultural Res Inst, Nanchong 637000, Sichuan, Peoples R China
4.Dong A Univ, Coll Nat Resources & Life Sci, Busan 49315, South Korea
期刊名称：JOURNAL OF NATURAL PRODUCTS （ 影响因子：4.05； 五年影响因子：4.603 ）
ISSN： 0163-3864
年卷期： 2021 年 84 卷 5 期
页码：
收录情况： SCI
摘要： 1-Deoxynojirimycin, an a-glucosidase inhibitor, possesses various biological activities such as antitumor, antidiabetic, and antiviral effects. However, the application of 1-deoxynojirimycin is restricted by its poor lipophilicity and low bioavailability. In this study, three 1-deoxynojirimycin derivatives (8-10) comprising 1-deoxynojirimycin and kaempferol were designed and synthesized to modify their pharmacokinetics and improve their antitumor efficacy. Among them, compound 10, a conjugate of 1-deoxynojirimycin and kaempferol linked through an undecane chain, exhibited excellent lipophilicity, antiproliferative effects, and alpha-glucosidase inhibitory activity. Compared with 1-deoxynojirimycin, kaempferol, and their combination, compound 10 downregulated cyclooxygenase-2 (COX-2) expression, arrested the cell cycle at the S phase, induced cellular apoptosis, and inhibited the migration of MCF-7 cells. Moreover, further investigation indicated that compound 10 induced MCF-7 cell apoptosis through a mitochondrial-mediated pathway via the loss of mitochondrial membrane potential. This led to increasing intracellular levels of reactive oxygen species (ROS) and Ca2+, the downregulation of Bcl-2 expression, and the upregulation of Bax levels.
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