Date of Defense
7-11-2024 2:00 PM
Location
F3-120
Document Type
Thesis Defense
Degree Name
Master of Science in Molecular Biology and Biotechnology
College
College of Science
Department
Biology
First Advisor
Dr. Yusra Al Dhaheri
Keywords
Capparis spinosa, clonogenicity, cell migration, metastasis, colorectal cancer, anticancer, autophagy, apoptos
Abstract
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers in the world. Plants are becoming a rich source of new anticancer compounds with novel targets. In this study, we evaluated the anticancer effects of Capparis spinosa on two CRC cell lines. HCT-116 and HT-29 CRC cells treated with various concentrations of C. spinosa leaf extract (CSLE) demonstrated inhibition of proliferation in a concentration-dependent manner. Additional analyses such as Western blot analysis, colony forming assay, and wound healing assay were performed to elucidate the mechanisms and pathways involved. The results revealed that non-cytotoxic concentrations of CSLE significantly inhibited the migration of the HCT-116 cells as shown by the wound-healing assay—the inhibition of the β-catenin pathway and downregulation of TNF-α encumbered cell migration. We also observed an accumulation of DNA double-stranded breaks (DSBs) as evidenced by increased levels of H2A.X. DSBs can trigger apoptosis and autophagy. Hence, we assessed the expression of autophagy-related proteins LC3, p62, and Beclin-1, revealing Beclin-1-independent autophagy. We also observed the induction of apoptosis evidenced by PARP cleavage with the subsequent activation of caspases 3/7. Moreover, CSLE also induced cell cycle arrest at the G1/S phase, concomitated with cyclin D1, cyclin E1, CDK2, and PCNA downregulation. Our findings identify C. spinosa as a promising chemo-preventive and therapeutic candidate that could modulate CRC growth and metastasis.
Included in
ANTICANCER ACTIVITY OF CAPPARIS SPINOSA EXTRACT AGAINST COLORECTAL CANCER
F3-120
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers in the world. Plants are becoming a rich source of new anticancer compounds with novel targets. In this study, we evaluated the anticancer effects of Capparis spinosa on two CRC cell lines. HCT-116 and HT-29 CRC cells treated with various concentrations of C. spinosa leaf extract (CSLE) demonstrated inhibition of proliferation in a concentration-dependent manner. Additional analyses such as Western blot analysis, colony forming assay, and wound healing assay were performed to elucidate the mechanisms and pathways involved. The results revealed that non-cytotoxic concentrations of CSLE significantly inhibited the migration of the HCT-116 cells as shown by the wound-healing assay—the inhibition of the β-catenin pathway and downregulation of TNF-α encumbered cell migration. We also observed an accumulation of DNA double-stranded breaks (DSBs) as evidenced by increased levels of H2A.X. DSBs can trigger apoptosis and autophagy. Hence, we assessed the expression of autophagy-related proteins LC3, p62, and Beclin-1, revealing Beclin-1-independent autophagy. We also observed the induction of apoptosis evidenced by PARP cleavage with the subsequent activation of caspases 3/7. Moreover, CSLE also induced cell cycle arrest at the G1/S phase, concomitated with cyclin D1, cyclin E1, CDK2, and PCNA downregulation. Our findings identify C. spinosa as a promising chemo-preventive and therapeutic candidate that could modulate CRC growth and metastasis.