2. Academic Validation
  3. N-desmethyldauricine from Menispermum dauricum DC suppresses triple-negative breast cancer growth in 2D and 3D models by downregulating the NF-κB signaling pathway

N-desmethyldauricine from Menispermum dauricum DC suppresses triple-negative breast cancer growth in 2D and 3D models by downregulating the NF-κB signaling pathway

  • Chem Biol Interact. 2024 Aug 1:398:111113. doi: 10.1016/j.cbi.2024.111113.
Wenting Liu 1,  Yan Yu 2,  Tao Hou 3,  Hongli Wei 2,  Fangbin Lv 4,  Aijin Shen 3,  Yanfang Liu 3,  Jixia Wang 5,  Dongmei Fu 6
Affiliations

Affiliations

  • 1 School of Biological Engineering, Dalian Polytechnic University, Dalian, 116034, China.
  • 2 Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
  • 3 Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang, 220000, China.
  • 4 Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang, 220000, China.
  • 5 Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; Jiangxi Provincial Key Laboratory for Pharmacodynamic Material Basis of Traditional Chinese Medicine, Ganjiang Chinese Medicine Innovation Center, Nanchang, 220000, China. Electronic address: jxwang@dicp.ac.cn.
  • 6 School of Biological Engineering, Dalian Polytechnic University, Dalian, 116034, China. Electronic address: dongmeifu@163.com.
PMID: 38908813 DOI: 10.1016/j.cbi.2024.111113
Abstract

Triple negative breast Cancer (TNBC) is the most aggressive subtype of breast Cancer, for which targeted therapy regimens are lacking. The traditional Chinese medicine Menispermum dauricum DC (M. dauricum) and its compounds have been reported to have antitumor activity against various cancers; however, their anti-TNBC activity is unknown. In this work, dauricine and N-desmethyldauricine from M. dauricum were separated and identified to have anti-TNBC via a multi-component bioactivity and structure-guided method. The cell counting kit 8 assay showed that dauricine and N-desmethyldauricine inhibited the proliferation of four tested TNBC cell lines, with half maximal inhibitory concentration values ranging from 5.01 μM to 13.16 μM. Further research suggested that N-desmethyldauricine induced cell Apoptosis, arrested cell cycle progression in the G0/G1 phase, and inhibited cell migration. Western blot analysis revealed that the proapoptotic protein cleaved-poly-ADP-ribose polymerase 1 was upregulated, and the G0/G1 phase-related proteins cyclin-dependent kinase 2 and cyclin D1 and the migration-related protein matrix metallopeptidase 9 were downregulated. Furthermore, N-desmethyldauricine decreased the protein expression of p65, an important subunit of nuclear factor kappa-beta (NF-κB). Moreover, an antiproliferation assay of three-dimensional (3D) tumor spheroids showed that N-desmethyldauricine diminished cell‒cell adhesion and suppressed the growth of TNBC 3D spheroids. Taken together, these findings indicate that N-desmethyldauricine inhibited the proliferation of TNBC cells and decreased the expression of p65 in the NF-κB pathway.

Keywords

3D tumor spheroids; M. dauricum; N-desmethyldauricine; NF-κB; TNBC.

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