1. Academic Validation
  2. Dual-Targeting Antiproliferation Hybrids Derived from 1-Deoxynojirimycin and Kaempferol Induce MCF-7 Cell Apoptosis through the Mitochondria-Mediated Pathway

Dual-Targeting Antiproliferation Hybrids Derived from 1-Deoxynojirimycin and Kaempferol Induce MCF-7 Cell Apoptosis through the Mitochondria-Mediated Pathway

  • J Nat Prod. 2021 May 28;84(5):1534-1543. doi: 10.1021/acs.jnatprod.1c00014.
Ran Zhang 1 2 Yueyue Zhang 1 Xiangdong Xin 1 Gaiqun Huang 1 3 Ning Zhang 1 Qinglei Zeng 1 Liumei Tang 1 Thomas Attaribo 1 Kwang Sik Lee 4 Byung Rae Jin 4 Zhongzheng Gui 1 2
Affiliations

Affiliations

  • 1 School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212100, People's Republic of China.
  • 2 Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang, Jiangsu 212100, People's Republic of China.
  • 3 Sericultural Research Institute, Sichuan Academy of Agricultural Sciences, Nanchong, Sichuan 637000, People's Republic of China.
  • 4 College of Natural Resources and Life Science, Dong-A University, Busan 49315, Republic of Korea.
Abstract

1-Deoxynojirimycin, an α-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 α-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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