Keio University · Chemistry
Professor Tadahiko Mashino's research lab focuses on the development of novel therapeutic agents targeting cancer drug resistance, with a particular emphasis on molecular mechanisms involving the Keap1-Nrf2 pathway and p62 signaling. The lab investigates bioactive nanomaterials, such as water-soluble fullerene derivatives, for their pro-apoptotic and reactive oxygen species (ROS)-modulating effects in cancer cells. A key research direction involves designing small molecules, like the Nrf2 inactivator K67, to overcome resistance in hepatocellular carcinoma and other malignancies. The lab integrates chemical synthesis, cell biology, and molecular pharmacology to identify and optimize compounds that restore drug sensitivity in resistant cancer cells.
Figures are computed from collected data and may differ slightly.
The biological activities of C(60)-bis(N,N-dimethylpyrrolidinium iodide), a water-soluble cationic fullerene derivative, on human promyeloleukaemia (HL-60) cells were investigated. The pyrrolidinium fullerene derivative showed cytotoxicity in HL-60 cells. The characteristics of apoptosis, such as DNA fragmentation and condensation of chromatin in HL-60 cells, were observed by exposure to the pyrrolidinium fullerene derivative. Caspase-3 and -8 were activated and cytochrome c was also released fr
Resistance to anticancer agents has been an obstacle to developing therapeutics and reducing medical costs. Whereas sorafenib is used for the treatment of human hepatocellular carcinoma (HCC), resistance limits its efficacy. p62, a multifunctional protein, is overexpressed in several HCC cell lines, such as Huh-1 cells. Phosphorylated p62 (<i>p</i>-p62) inhibits the protein-protein interaction (PPI) between Keap1 and Nrf2, resulting in the Nrf2 overactivation that causes drug resistance. We have
Open papers in the app to read, cite, and organize with AI.
