Topoisomerase I inhibitor 5 is an efficient topoisomerase I inhibitor with an IC50 value, effectively disrupting DNA and inhibiting topoisomerase I activity. It induces apoptosis in MCF-7 cells and arrests the cell cycle at the G1 phase, displaying potency in reversing P-gp-mediated resistance to Adriamycin [1].

Topoisomerase I inhibitor 5 (compound 14) demonstrates significant antiproliferative effects against various cancer cell lines at concentrations ranging from 0 to 50 μM over 48 hours while exhibiting lower cytotoxicity towards normal LO2 cells. At concentrations of 2 to 8 μM for 24 hours, it triggers G1 phase cell cycle arrest in MCF-7 cells and increases apoptotic rates in both MCF-7 and MCF-7/ADR cells over 48 hours. Additionally, it elevates the expression of apoptosis-inducing proteins cleaved-caspase-3 and cleaved-PARP in MCF-7 cells and modifies the expression of anti-apoptotic and pro-apoptotic proteins in MCF-7/ADR cells within 24 hours. Notably, at low doses (0.1 μM for 24 hours), it induces apoptosis through ROS accumulation in MCF-7/ADR cells. Furthermore, it enhances the intracellular accumulation of ADR and Rh123 in MCF-7/ADR cells and reduces P-gp expression, indicating decreased drug resistance mechanisms. Detailed cell proliferation assays revealed IC50 values showing the compound's efficacy across several cancer cell types with minimal impact on normal cells, underscoring its potential as a selective cancer therapeutic agent [1].

Intravenous administration of the Topoisomerase I inhibitor 5 at doses of 1 mg/kg and 10 mg/kg every two days for a period of 21 days resulted in a significant decrease in tumor growth in an animal model utilizing Balb/c nude mice, which were injected with 10^6 MCF-7 cells in the left flank for 7 days. Notably, the tumor inhibition ratio reached 32.4% at a dosage of 1 mg/kg and 7.2% at 10 mg/kg, highlighting the compound's efficacy in reducing tumor size.