THE CYTOTOXIC COMPOUNDS OF FRACTIONATED EXTRACT OF TIBIG (FICUS NOTA) LEAVES AGAINST HCT116 HUMAN COLORECTAL CARCINOMA CANCER LINE

Aguilar, K. M. B., Andres, F. N. Q., Celis, V. E. Y. P., Cobico, K. A., De Jesus, C. Q., Mariano, F. J. B.*, Andal, Mylene S., RPh, MS Pharm

Introduction: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths, with early detection often hindered by the absence of initial symptoms. Natural sources like Ficus species offer potential alternatives for cancer treatment, yet studies on Ficus nota remain limited. This study aimed to identify the most cytotoxic fraction of Ficus nota extract and evaluate its cytotoxic activity. Methodology: The plant was authenticated, dried, macerated, and extracted, followed by phytochemical screening, solvent partitioning, and gravity column chromatography. Fractionation was guided by the Brine Shrimp Lethality Assay (BSLA) and MTT Assay, LC-MS/MS identified compounds in the most active fraction, and molecular docking was used to assess their potential binding interactions with cancer-related targets. Results: BSLA showed that the 1000 ppm hexane partition exhibited the highest cytotoxicity, while the MTT Assay revealed the 2:8 fraction as the most active. The extract exhibited moderate cytotoxicity against HCT 116, with an IC₅₀ comparable to Vinblastine and a selectivity index above 1, suggesting cancer cell specificity. LC-MS/MS detected 18 potentially cytotoxic compounds, the most abundant being Phytolacca Cerebroside and Neoline. Discussion: Molecular docking revealed strong multi-target interactions with TNIK, PI3Kα, and EGFR, particularly from Phytolacca Cerebroside, which showed exceptional binding energies but poor drug-like properties due to high lipophilicity and low solubility. In contrast, Neoline showed consistently strong binding and favorable ADME characteristics, making it a more promising lead for drug development.