School of Science Division of Life Science 26 Potential Cancer Drug Identification and Characterization Supervisor: LIANG Chun / LIFS Student: KO Ching Chi / BCB Course: UROP 1100, Spring Cancer therapies often lack selectivity, damaging healthy cells. This study investigates EN002, a novel drug targeting pre-replicative complex (pre-RC) assembly, to evaluate its cancer-specific cytotoxicity. Using cell cycle analysis and molecular profiling in normal (RPE1) and cancerous (HeLa, HCT116) cells, EN002 demonstrated selective effects: it arrested normal cells in G1 phase while driving cancer cells into abortive S-phase progression, ultimately inducing apoptosis. Mechanistically, differential regulation of pre-RC components (e.g., CDC6) and cell cycle regulators underpinned this selectivity. These findings highlight EN002’s potential as a targeted therapy by exploiting pre-RC vulnerabilities in cancer, minimizing off-target toxicity. Further studies are needed to elucidate downstream signaling pathways. Potential Cancer Drug Identification and Characterization Supervisor: LIANG Chun / LIFS Student: SUN Ming Hong / CPEG Course: UROP 1100, Summer A compound nicknamed M2 was found to have significant anticancer activities by inhibiting DNA replication, with a lower toxicity towards normal cells. Half maximal inhibitory concentration (IC50) of M2 and its derivatives is measured in this UROP project. The derivatives of M2 have two generations. AA299 is first generation and 423,459 is second generation. In this process, Cervical cancer cells (Hela) are mixed with different concentrations of M2 and its derivatives to observe the cancer cell viability using Cell Counting Kit8 (CCK8). Graphpad prism is used to draw the cell viability graph and calculate IC50 after obtaining obs data. A total of 96 hours is spent in this experiment. The final findings is that all derivatives of M2 have smaller IC50 than M2 and derivatives show different IC50 depending on its unequal structure. Data of IC50 and cell viability graph provide basis for following experiments and straightly show the effect of drugs. Potential Cancer Drug Identification and Characterization Supervisor: LIANG Chun / LIFS Student: YE Jiaxin / BCB Course: UROP 1000, Summer DNA replication in eukaryotic cells is strictly controlled to ensure genetic integrity. Cancer drug research targets DNA replication initiation proteins as promising anticancer targets. The knockdown of the MCM complex, which is essential for pre-replicative complexes, disrupted chromatin binding of other pre-RC proteins, causing DNA defects and apoptosis in the S phase. Two investigated drugs target this mechanism, but their potency remains unclear. To evaluate their potency, I and others in the laboratory, conducting a cell counting kit-8 (CCK-8) assay and compared the viability of HeLa cells treated with varying concentrations of two drugs, providing insights into their efficacy. Further analysis of the CCK-8 assay result would surely advance our understanding of cell viability during drug treatment.
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