Pharmacological Drugs Aimed at Preventing Cancer Cell Division

Abstract

The complex replication cycle of cancer is known to have properties that deregulate cell division. A potential therapeutic application has been discovered through a CYCLOPS model using combinations of pharmacological drugs at multiple sites in the cell cycle. In human cell division this approach gains insight into the checkpoint of G1-S, the Spindle Assembly Regulator, and apoptosis. Palbociclib, Gemcitabine, Paclitaxel, and Actinomycin D are the four drugs used to show possible sites to stimulate cancer cell apoptosis, due to small discrepancy between MiaPaca-2 (pancreatic carcinoma) and ARPE-19 (retina “normal” cells). Cancer treatments currently can have severe consequences on normal cells because the medications cannot distinguish harmful cells from healthy ones. This application model separates cells by a drug induced arrest, which could have major benefits to signaling specific cancer apoptosis. This could be significant in predicting the effect of anticancer drugs on oncogenic genes to maximize lethality, while minimizing normal tissue death (Jackson et al., 2017). Palbociclib is non-cytotoxic and places an arrest on the G1 phase causing a roadblock into the Synthesis phase for ARPE-19. MiaPaca-2 cells override this arrest to continue the cell division process; however, the cancer cells will be eliminated by Gemcitabine, a Synthesis (S) phase specific drug. Palbociclib in combination with delayed addition of Gemcitabine leads to a marginal difference making it a potential differentiator for pharmacological drugs to prevent further cancer cell division (Jackson et al., 2017). The researchers studied a second target site SAC using Paclitaxel, which collects cells in the Mitotic (M) phase, and Actinomycin D, a transcription inhibitor that functions to kill all cells not in the M phase. This second target site did not result in statistically significant results, which leads to an unanswered question of if this application model can be broadened to prevent cancer cell division in multiple sites and cell lines.