Unlocking the Potential: Integrative Effects of 5-Fluorouracil and Epigallocatechin-3-Gallate on Colorectal Cancer Stem Cell Regulation
نویسندگان
1 Department of Health and Medicine Doctoral Program, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
2 Department of Biochemistry and Molecular Biology, Faculty of Medicine, Soegijapranata Catholic University, Semarang, Indonesia
3 Department of Postgraduate Biomedical Science, Faculty of Medicine, Sultan Agung Islamic University (UNISSULA), Semarang, Indonesia
4 Department of Surgery, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
5 Division of Haematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
6 Stem Cell and Cancer Research (SCCR) Laboratory, Semarang, Indonesia
doi
10.26655/JMCHEMSCI.2024.11.12چکیده
5-Fluorouracil (5-FU) is the backbone treatment of colorectal cancer (CRC) for years. However, this modality is effective only for some type of tumors due to Colorectal cancer stem cells (CR-CSCs) drug-resistance property. CR-CSCs have been considered as the main contributor to cancer progression. Therefore, it is a promising therapeutic target for anticancer agents in CRC. Epigallocatechin-3-gallate (EGCG) is a polyphenol phyto-compound that inhibits CSC growth and stemness in various cancers. Thus, we innovated in novel therapeutic strategies by combining chemotherapeutic agents and natural compounds to improve anticancer treatment. This study was designed to analyze the integrative effect of 5-FU and EGCG in reducing populations, proliferation, stemness properties, and increasing apoptosis of CR-CSCs through in vitro study. CR-CSCs CD44+/CD133+ from HCT-116 were used in this study. We studied the effect of 5-FU and EGCG in vitro. Flow cytometry analysis was used to quantify the CR-CSCs cell cycle and apoptosis profile. Protein expressions of Bcl-2 were detected by western blotting assay. CCND1, Nanog and Wnt3a mRNA expression were analyzed by qPCR. Combination of 5-FU+EGCG increased S-phase cell cycle arrest and apoptosis compared to 5-FU only. The results showed that Bcl-2 and Wnt3a were decreased in a 5-FU+EGCG group than 5-FU only. However, there were no significant differences in CCND1 and Nanog gene expression compared with 5-FU. 5-FU and EGCG may interactively reduce proliferation, increase apoptosis, and inhibit Wnt signaling, but not down-regulate stemness of CR-CSCs in vitro.
