School of Science Division of Life Science 23 Potential Cancer Drug Identification and Characterization Supervisor: LIANG, Chun / LIFS Student: CHAN, Kwing Hei / BIBU Course: UROP1100, Spring Given that cancer is a significant burden of disease worldwide, there is an urgent need for us todevelop an effective anticancer therapy which can minimize the side effects caused on patients. During cell replication, a protein complex named pre-replicative complex (pre-RC) plays an important role in regulating DNA replication initiation. More importantly, the MiniChromosome Maintenance (MCM) complex is one of the core members of the pre-RC, which plays a crucial role in the successful initiation and elongation of DNA replication. We are currently developing small molecules that may target pre-RC as novel anticancer agents. A compound nicknamed CM2 was found to have significant anticancer activities by inhibiting DNA replication, with a lower toxicity towards normal cells. In this study, we aimed at first confirming the anticancer activity of CM2 by performing WST-1 assay. We further examined the ability of CM2 in inhibiting the pre-RC by performing chromatin binding assay. In order to further elucidate the working mechanism of CM2, we also looked for suitable way of synchronizing normal and cancer cells, in which we tested whether contact inhibition occurs in different cell lines by first observing the growth of cells after reaching 100% confluence, followed by performing Western blotting to investigate the expression of cell cycle related proteins. Finally, we tested for the drug activity under different conditions by checking for the sensitivity of the cell lines to CM2 during or after contact inhibition. Potential Cancer Drug Identification and Characterization Supervisor: LIANG, Chun / LIFS Student: SILVA, Paolo Mendoza / BIBU Course: UROP1000, Summer The treatment of cancer has long been a question that science has had no perfect answers to. Cancer cells nature as mutated human cells that can escape the immune system and by the same nature many drugs which killed cancer cells harm to normal cells as well. No matter how effective the anti-cancer drugs against cancer cells if it is as toxic to normal cells the treatment would be of great risk to the patient. Chemotherapy is the most common treatment method of cancer however it has many drawbacks to the patient, such as non-selectivity, weakened immune system and various other side effects. This paper aims to study a novel anti-cancer drug called NJ4 that has the potential ability to target the pre-RC protein which assembling in G1 phase. Since cancer cells are continually proliferating themselves, so only cancer cells need to synthesis large amount of pre-RC proteins that can lead the drug accumulating in the cancer cell, thereby protecting normal cells. In this study, we finding its effective concentration, selectivity and effective period in the cell cycle.
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