DNA interactive property of poly‐L‐lysine induces apoptosis in MCF‐7 cells through DNA interaction

Abstract

AbstractPoly‐L‐lysine (PLL) is known to be an encapsulating agent in drug formulation and delivery. PLL also has apoptotic and antiproliferative activities that enable blocking of the tumorigenesis process. However, the dose‐selective activities of PLL in exerting apoptosis against cancer are unclear. Therefore, this study has been designed to explore the potential role and dose of PLL in apoptosis, if any. For this, PLL was administered at several doses in cancer cell lines and was found to be more potent against MCF‐7 cells. PLL causes mitochondria‐mediated apoptotic death through the upregulation of cleaved caspase‐3. To investigate the mechanism responsible for this activity, we have analyzed if PLL could have the DNA interactive property or not. For this, molecular docking analysis was carried out to prove whether it has the property to bind with DNA or not. Studies have revealed that PLL is a potent DNA binder and it probably performs such apoptotic activities through the binding of cellular DNA early in an exposure. Simultaneous upregulation of both ROS‐mediated stress and also in key protein expressions like γ‐H2AX could also help us to confirm that PLL induces apoptosis through DNA interaction. This finding leads us to believe that PLL could play an interfering role with other chemotherapeutic compounds when used as a drug‐coating material as it exerts an apoptotic effect on cancer cells, which should be avoided by using a much lower concentration.