Date of Defense
12-6-2025 10:00 AM
Location
F3-127
Document Type
Thesis Defense
Degree Name
Master of Science in Molecular Biology and Biotechnology
College
COS
Department
Biology
First Advisor
Prof. Rabah Iratni
Keywords
Colorectal Cancer, Chromene Derivatives, Multinucleation, Cell Cycle Arrest, DNA Damage, Senescence, Apoptosis.
Abstract
Colorectal cancer (CRC) stands as the third most common cancer globally, accounting for nearly 10% of all newly diagnosed cancer cases. In the UAE, CRC was ranked as the third most frequently diagnosed malignancy, and the leading cause of cancer-associated deaths in 2023. Standard CRC treatment strategies include surgical resection, chemotherapy, immunotherapy, targeted therapy, or a combination of all, depending on the cancer stage and molecular profile. Despite these interventions, disease recurrence is experienced by a considerable number of cancer patients. Hence, there is an urgent need to develop novel alternative treatments to overcome poor prognosis. Recently, cancer research has revealed the therapeutic potential of synthetic molecules, especially those that structurally mimic natural products. Among these, chromenes have demonstrated anticancer properties alongside a spectrum of other pharmacological activities. In the present study, human CRC cell lines, HCT-116, HT-29, and Caco-2, were used to assess the anticancer potential of a new synthetic chromene derivative (C4) in vitro. C4 demonstrated a time- and concentration-dependent inhibition of the proliferation of CRC cells. All subsequent mechanistic investigations were performed on the HCT-116 cell line, as it exhibited the highest sensitivity to the drug. C4 inhibited the formation and growth of HCT-116 colonies. Further, microscopic examination following treatment with C4 demonstrated cell multinucleation, a sign of possible mitotic catastrophe. Additionally, C4 caused a G2/M arrest in HCT-116 cells, accompanied by an increase in the levels of H3pSer10. C4 also led to the accumulation of γH2AX as a result of DNA damage induction. Moreover, senescence was observed as marked by positive senescence-associated β-galactosidase staining and the upregulation of cyclin-dependent kinase inhibitors, p21 and p16. Furthermore, C4 triggered apoptosis by modulating both intrinsic and extrinsic apoptotic pathways. Overall, these findings confirm that our novel synthetic chromene derivative has a potent anti-CRC activity and therefore holds a promising therapeutic value for treating CRC.
Included in
Biology Commons, Cell Biology Commons, Molecular Biology Commons
THE ANTICANCER ACTIVITY OF NOVEL CHROMENE DERIVATIVES AGAINST COLORECTAL CANCER CELLS
F3-127
Colorectal cancer (CRC) stands as the third most common cancer globally, accounting for nearly 10% of all newly diagnosed cancer cases. In the UAE, CRC was ranked as the third most frequently diagnosed malignancy, and the leading cause of cancer-associated deaths in 2023. Standard CRC treatment strategies include surgical resection, chemotherapy, immunotherapy, targeted therapy, or a combination of all, depending on the cancer stage and molecular profile. Despite these interventions, disease recurrence is experienced by a considerable number of cancer patients. Hence, there is an urgent need to develop novel alternative treatments to overcome poor prognosis. Recently, cancer research has revealed the therapeutic potential of synthetic molecules, especially those that structurally mimic natural products. Among these, chromenes have demonstrated anticancer properties alongside a spectrum of other pharmacological activities. In the present study, human CRC cell lines, HCT-116, HT-29, and Caco-2, were used to assess the anticancer potential of a new synthetic chromene derivative (C4) in vitro. C4 demonstrated a time- and concentration-dependent inhibition of the proliferation of CRC cells. All subsequent mechanistic investigations were performed on the HCT-116 cell line, as it exhibited the highest sensitivity to the drug. C4 inhibited the formation and growth of HCT-116 colonies. Further, microscopic examination following treatment with C4 demonstrated cell multinucleation, a sign of possible mitotic catastrophe. Additionally, C4 caused a G2/M arrest in HCT-116 cells, accompanied by an increase in the levels of H3pSer10. C4 also led to the accumulation of γH2AX as a result of DNA damage induction. Moreover, senescence was observed as marked by positive senescence-associated β-galactosidase staining and the upregulation of cyclin-dependent kinase inhibitors, p21 and p16. Furthermore, C4 triggered apoptosis by modulating both intrinsic and extrinsic apoptotic pathways. Overall, these findings confirm that our novel synthetic chromene derivative has a potent anti-CRC activity and therefore holds a promising therapeutic value for treating CRC.