Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway
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 mechan...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3904 |
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| author | Yi-Fen Chiang Ko-Chieh Huang Hsin-Yuan Chen Nadia M. Hamdy Tsui-Chin Huang Hsin-Yi Chang Tzong-Ming Shieh Yun-Ju Huang Shih-Min Hsia |
| author_facet | Yi-Fen Chiang Ko-Chieh Huang Hsin-Yuan Chen Nadia M. Hamdy Tsui-Chin Huang Hsin-Yi Chang Tzong-Ming Shieh Yun-Ju Huang Shih-Min Hsia |
| author_sort | Yi-Fen Chiang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T10:43:38Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:43:38Z |
| publishDate | 2024-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-abb15068975644d3a49e86a4ba21b6fb2024-04-12T13:20:05ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257390410.3390/ijms25073904Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 PathwayYi-Fen Chiang0Ko-Chieh Huang1Hsin-Yuan Chen2Nadia M. Hamdy3Tsui-Chin Huang4Hsin-Yi Chang5Tzong-Ming Shieh6Yun-Ju Huang7Shih-Min Hsia8School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, TaiwanBiochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo 11566, EgyptGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110301, TaiwanGraduate Institute of Medical Science, National Defense Medical Center, Taipei 11490, TaiwanSchool of Dentistry, College of Dentistry, China Medical University, Taichung 40402, TaiwanDepartment of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan City 710301, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, TaiwanBreast 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.https://www.mdpi.com/1422-0067/25/7/3904breast cancer stem cellhinokitiolapoptosisautophagyCD44 |
| spellingShingle | Yi-Fen Chiang Ko-Chieh Huang Hsin-Yuan Chen Nadia M. Hamdy Tsui-Chin Huang Hsin-Yi Chang Tzong-Ming Shieh Yun-Ju Huang Shih-Min Hsia Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway International Journal of Molecular Sciences breast cancer stem cell hinokitiol apoptosis autophagy CD44 |
| title | Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway |
| title_full | Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway |
| title_fullStr | Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway |
| title_full_unstemmed | Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway |
| title_short | Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway |
| title_sort | hinokitiol inhibits breast cancer cells in vitro stemness progression and self renewal with apoptosis and autophagy modulation via the cd44 nanog sox2 oct4 pathway |
| topic | breast cancer stem cell hinokitiol apoptosis autophagy CD44 |
| url | https://www.mdpi.com/1422-0067/25/7/3904 |
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