Anti-Cancer Potential of Isoflavone-Enriched Fraction from Traditional Thai Fermented Soybean against Hela Cervical Cancer Cells

• Published in: International journal of molecular sciences 2024-09, Vol.25 (17), p.9277
• Main Authors: Sukhamwang, Amonnat, Inthanon, Sirinada, Dejkriengkraikul, Pornngarm, Semangoen, Tistaya, Yodkeeree, Supachai
• Format: Article
• Language: English
• Subjects: Antigens; Apoptosis; Apoptosis - drug effects; Breast cancer; Cancer therapies; Cell cycle; Cell death; Cell growth; Cell Proliferation - drug effects; Cervical cancer; Chemotherapy; Clinical trials; Cytotoxicity; daidzein; Fermentation; fermented soybean; Fibroblasts; Functional foods & nutraceuticals; genistein; Glycine max - chemistry; HeLa Cells; human cervical carcinoma cells; Humans; invasion; Isoflavones - pharmacology; Metastasis; Peptides; Plant Extracts - chemistry; Plant Extracts - pharmacology; Prostate cancer; Proteins; Side effects; Soybeans; Womens health
• ISSN: 1661-6596; 1422-0067; 1422-0067
• DOI: 10.3390/ijms25179277

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.