2. Academic Validation
  3. Arnicolide C Suppresses Tumor Progression by Targeting 14-3-3θ in Breast Cancer

Arnicolide C Suppresses Tumor Progression by Targeting 14-3-3θ in Breast Cancer

  • Pharmaceuticals (Basel). 2024 Feb 8;17(2):224. doi: 10.3390/ph17020224.
Zhengrui Liu 1,  Xiaodan Lyu 1,  Jiaxu Chen 2,  Benteng Zhang 1,  Siman Xie 1,  Yan Yuan 3,  Li Sun 1,  Shengtao Yuan 4,  Hong Yu 5,  Jian Ding 4 6,  Mei Yang 1
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
  • 2 College of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • 3 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 4 Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
  • 5 Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, China.
  • 6 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
PMID: 38399439 DOI: 10.3390/ph17020224
Abstract

Background: Arnicolide C, which is isolated from Centipeda minima, has excellent antitumor effects. However, the potential impacts and related mechanisms of action of arnicolide C in breast Cancer remain unknown. Methods: The viability of breast Cancer cells was measured using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and colony formation assays. For analysis of Apoptosis and the cell cycle, flow cytometry was used. A molecular docking approach was used to explore the possible targets of arnicolide C. Western blot analysis was used to detect changes in the expression of 14-3-3θ and proteins in related pathways after arnicolide C treatment in breast Cancer cells. The anti-breast Cancer effect of arnicolide C in vivo was evaluated by establishing cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Results: Arnicolide C inhibited proliferation, increased Apoptosis, and induced G1 arrest. In particular, molecular docking analysis indicated that arnicolide C binds to 14-3-3θ. Arnicolide C reduced 14-3-3θ expression and inhibited its downstream signaling pathways linked to cell proliferation. Similar results were obtained in the CDX and PDX models. Conclusion: Arnicolide C can have an anti-breast Cancer effect both in vitro and in vivo and can induce cell cycle arrest and increase Apoptosis in vitro. The molecular mechanism may be related to the effect of arnicolide C on the expression level of 14-3-3θ. However, the specific mechanism through which arnicolide C affects 14-3-3θ protein expression still needs to be determined.

Keywords

14-3-3θ; PDX; arnicolide C; breast neoplasms; cell proliferation.

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