Arwa Ishaq A Khayyat1,2* 1 Department of Biochemistry, College of Science, King Saud University, P.O. Box2455, Riyadh 11451, Saudi Arabia *Corresponding author’s email: aalkhyyat@ksu.edu.sa Received: 20 May 2025 / Accepted: 23 September 2025 / Published Online: 29 September 2025 Abstract Syzygium aromaticum exhibits diverse pharmacological activities due to its antioxidant potential. Therefore, this study addressed the mechanisms of S. aromaticum extract (SAE) treatment on HT-29 cells proliferation. SAE has an adequate content of phytochemicals. The IC50 of SAE for HT-29 cells was calculated to be 137.81 ± 1.25 µg/ml after 48 hours. Treatment with SAE showed significant increase in the percentage of apoptotic HT-29 cells, with significant increase in their count in the G0/1 and S-phases, along with significant decrease in the G2/M phase. Significant downregulations of the Hh, Wnt-4, and PDGFR-β genes was represented in the colorectal cell lines (HT-29) after treatment with SAE. Collectively, these results demonstrate that SAE inhibits HT-29 cell proliferation by activating apoptosis and interfering with cilia signal transduction, highlighting its potential as a natural therapeutic candidate against colorectal cancer. Keywords: Syzygium aromaticum extract, Colorectal cancer, Cell proliferation, Apoptosis, Cell cycle, Cilia signal transduction | 
