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您的检索式：作者名="Alissar Monzer"
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| 1 | Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and threedimensional in vitro models显示文摘BACKGROUND Colorectal cancer(CRC) is the second leading cause of cancer-related mortality.Cancer stem cells(CSCs) in CRC, which are spared by many chemotherapeutics,have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone(DIQ) has shown promising effects on targeting colon cancer.However, there is limited research on the effects of DIQ on eradicating CSCs in CRC.AIM To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional(2D) and three-dimensional(3D) models using colonospheres and patient-derived organoids.METHODS Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays,immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model.RESULTS Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116and HT29 stem/progenitor cells at sub-toxic doses of 1 μmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related-catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions.CONCLUSION This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation. | Alissar Monzer Kevork Wakimian Farah Ballout Samar Al Bitar Amani Yehya Mariam Kanso Nour Saheb Ayman Tawil Samer Doughan Maher Hussein Deborah Mukherji Walid Faraj Hala Gali-Muhtasib Wassim Abou-Kheir | 2022 | World Journal of Gastroenterology2022，28，33： | 1 |
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