| Autor: |
Sukhamwang A; Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand., Inthanon S; Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand., Dejkriengkraikul P; Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.; Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand., Semangoen T; Department of Medical Technology, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand., Yodkeeree S; Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.; Anticarcinogenesis and Apoptosis Research Cluster, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2024 Aug 27; Vol. 25 (17). Date of Electronic Publication: 2024 Aug 27. |
| DOI: |
10.3390/ijms25179277 |
| Abstrakt: |
Cervical cancer is a leading cause of gynecological malignancies and cancer-related deaths among women worldwide. This study investigates the anti-cancer activity of Thua Nao, a Thai fermented soybean, against HeLa cervical carcinoma cells, and explores its underlying mechanisms. Our findings reveal that the ethyl acetate fraction of Thua Nao (TN-EA) exhibits strong anti-cancer potential against HeLa cells. High-performance liquid chromatography (HPLC) analysis identified genistein and daidzein as the major isoflavones in TN-EA responsible for its anti-cancer activity. TN-EA and genistein reduced cell proliferation and induced G2/M phase arrest, while daidzein induced G1 arrest. These responses were associated with the downregulation of cell cycle regulators, including Cyclin B1, cycle 25C (Cdc25C), and phosphorylated cyclin-dependent kinase 1 (CDK-1), and the upregulation of the cell cycle inhibitor p21. Moreover, TN-EA and its active isoflavones promoted apoptosis in HeLa cells through the intrinsic pathway, evidenced by increased levels of cleaved Poly (ADP-ribose) polymerase (PARP) and caspase-3, loss of mitochondrial membrane potential, and the downregulation of anti-apoptotic proteins B-cell leukemia/lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xL), cellular inhibitor of apoptosis proteins 1 (cIAP), and survivin. Additionally, TN-EA and its active isoflavones effectively reduced cell invasion and migration by downregulating extracellular matrix degradation enzymes, including Membrane type 1-matrix metalloproteinase (MT1-MMP), urokinase-type plasminogen activator (uPA), and urokinase-type plasminogen activator receptor (uPAR), and reduced the levels of the mesenchymal marker N-cadherin. At the molecular level, TN-EA suppressed STAT3 activation via the regulation of JNK and Erk1/2 signaling pathways, leading to reduced proliferation and invasion of HeLa cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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