2. Academic Validation
  3. Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway

Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway

  • Int J Mol Sci. 2024 Mar 31;25(7):3904. doi: 10.3390/ijms25073904.
Yi-Fen Chiang 1,  Ko-Chieh Huang 1,  Hsin-Yuan Chen 1,  Nadia M Hamdy 2,  Tsui-Chin Huang 3,  Hsin-Yi Chang 4,  Tzong-Ming Shieh 5,  Yun-Ju Huang 6,  Shih-Min Hsia 1 7 8 9 10
Affiliations

Affiliations

  • 1 School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan.
  • 2 Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, Egypt.
  • 3 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, Taiwan.
  • 4 Graduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, Taiwan.
  • 5 School of Dentistry, College of Dentistry, China Medical University, Taichung 40402, Taiwan.
  • 6 Department of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan City 710301, Taiwan.
  • 7 School of Food and Safety, Taipei Medical University, Taipei 110301, Taiwan.
  • 8 Nutrition Research Center, Taipei Medical University Hospital, Taipei 110301, Taiwan.
  • 9 Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan.
  • 10 TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 110301, Taiwan.
PMID: 38612715 DOI: 10.3390/ijms25073904
Abstract

Breast Cancer (BC) represents one of the most prevalent malignant threats to women globally. Tumor relapse or metastasis is facilitated by BC stemness progression, contributing to tumorigenicity. Therefore, comprehending the characteristics of stemness progression and the underlying molecular mechanisms is pivotal for BC advancement. Hinokitiol (β-thujaplicin), a tropolone-related compound abundant in the heartwood of cupressaceous Plants, exhibits antimicrobial activity. In our study, we employed three BC cell lines (MDA-MB-231, MCF-7, and T47D) to assess the expression of stemness-, apoptosis-, and autophagy-related proteins. Hinokitiol significantly reduced the viability of Cancer cells in a dose-dependent manner. Furthermore, we observed that hinokitiol enhances Apoptosis by increasing the levels of cleaved poly-ADP-ribose polymerase (PARP) and phospho-p53. It also induces dysfunction in Autophagy through the upregulation of LC3B and p62 protein expression. Additionally, hinokitiol significantly suppressed the number and diameter of Cancer cell line spheres by reducing the expression of cluster of differentiation44 (CD44) and key transcription factors. These findings underscore hinokitiol's potential as a therapeutic agent for breast Cancer, particularly as a stemness-progression inhibitor. Further research and clinical studies are warranted to explore the full therapeutic potential of hinokitiol in the treatment of breast Cancer.

Keywords

CD44; apoptosis; autophagy; breast cancer stem cell; hinokitiol.

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