Fraction Derived from Lansium domesticum Leaves Triggers Cell Cycle Arrest and Apoptosis in 4T1 Cell Line Via Cdk-2 and p53 proteins modulation

This study investigates the anticancer potential of ethanolic extracts (EEL) and fractions derived from Lansium domesticum leaves, with a particular focus on the fourth fraction of EEL (EELD), against the murine 4T1 breast cancer cell line. EELD demonstrated significant cytotoxic activity, with an IC₅₀ of 72.75 ± 2.98 µg/mL and a selectivity index (SI) of 4.69, indicating notable selectivity toward cancer cells compared to normal cells. Flow cytometry analysis revealed that EELD induced cell cycle arrest at the Sub G1 phase and promoted apoptosis in a dose-dependent manner. Immunocytochemical evaluation showed upregulation of p53 and suppression of Cdk-2 expression, highlighting the involvement of intrinsic apoptotic pathways. Phytochemical analysis identified bioactive compounds, including hexadecanoic acid, methyl ester, and trans-13-octadecenoic acid, methyl ester, which are associated with anticancer and antioxidant properties. These findings suggest that EELD’s anticancer activity is mediated through a combination of cell cycle regulation, apoptosis induction, and bioactive compound synergy. While EELD exhibits promising anticancer properties, its efficacy remains lower than the standard chemotherapeutic agent doxorubicin. Further, in vivo studies and molecular investigations are required to optimize its therapeutic potential and elucidate its mechanisms of action. This study highlights the potential of L. domesticum as a source of plant-derived anticancer agents and provides a foundation for future research into its therapeutic applications.