IDENTIFICATION OF A POTENT AUTOPHAGY INHIBITOR IN LUNG AND BREAST CANCER

Abstract

The incidence rate of both breast and lung cancer has escalated along with increased recurrence cases despite new treatment regimens. The inhibition of autophagy by particular medicines is a unique technique for broadening the range of treatment resistance in both of these cancers. The aim of the present investigation is to identify a potent autophagy inhibitor in lung and breast cancer. Different anti-malarial drugs were evaluated through in silico tools for their autophagy inhibiting potential in lung and breast cancer. Through a detailed text mining approach, a database of vital genes involved in autophagy in lung and breast cancer was curated. Molecular docking of these targets with different anti-malarial drugs was performed using AutoDock and AutoDock Vina. Mefloquine exhibited the best affinity towards all targets in lung cancer and hence it was chosen for further in vitro validation in A549 cells. Similarly, Artemisinin was selected for further in vitro evaluation in MCF-7 cells. When A549 cells were treated with varied concentrations of Mefloquine, significant cell death was observed with increased concentrations of drug and the IC50 of Mefloquine was determined to be 6.315 μM for 24 hrs. MCF-7 cells too showed cell death when treated with Artemisinin and the IC50 value obtained for the drug was found to be 1.138μM for 72 hrs. Based on these investigations, we can state conclusively that Mefloquine and Artemisinin appear to be potential autophagy inhibiting candidates for therapeutic treatment of lung and breast cancer respectively, in comparison to other known drugs.