Research Projects

Cancer is a disease characterized by genetic alterations that lead to loss of cell cycle control and genome instability. These mutations in genes of crucial regulatory pathways, such as DNA damage response, cell cycle checkpoints, and oxidative stress response, cause cancer cells to be genetically unstable. Anti-cancer drugs often exploit these differences to induce cytotoxicity. Lycorine, a natural Amarillidaceae alkaloid, has been explored for its anti-microbial, anti-viral, and anti-inflammatory properties. However, the mechanism through which it induces selective cytotoxicity in cancer cells remains elusive. Lycorine's ability to bind to DNA and induce ROS-mediated apoptosis suggests it may induce direct or ROS-mediated DNA damage. It is also a potent eukaryotic translation inhibitor, with defects in tRNA modifications mediated translation dysregulation being a new Achilles' heel for many cancer cells. Translation inhibitors such as didemnin, cycloheximide, paromomycin, lactimidomycin, and homoharringtonine have been reported to sensitize cancer cell lines, with homoharringtonine receiving FDA approval for its use in cancer therapy. This study aims to evaluate the cytotoxic potential of lycorine using yeast and mammalian cancer cells deficient in DNA repair pathway genes and translation regulation genes. The researchers aim to determine the targets of lycorine by selecting and studying its cytotoxic effect on DNA damage response pathway and translation regulation deficient mutant yeast strains.