Identification of novel inhibitors from Urtica spp against MDAMB-231 targeting JAK 2 receptor for breast cancer therapy

Abstract

Abstract Breast cancer is the most prevalent form of cancer in women globally, and MDA-MB-231 or TNBC (Triple-negative breast cancer) is its aggressive type since it lacks the usual targets. JAK2/STAT3 pathway can be an important lead in anticancer drug discovery, as restraining the downstream signalling of this pathway results in the induction of cell apoptosis. Moreover, various limitations associated with chemotherapy are the reason to find an alternative herbal-based therapy. For this study, we collected Urtica dioica, and U. parviflora from different regions of Uttarakhand, followed by preparation of their leaf and stem extracts in different solvents. The GC-MS analysis of these extracts revealed a total of 173 compounds to be present in them. Further, by molecular docking approach, we studied the interaction between these compounds and JAK2, and 12 major compounds with better binding energy than the control Paclitaxel were identified. In addition, the selected hits were also reported to display better pharmacokinetic properties. The anticancer potential of these extracts was also evaluated by in vitro approach in the MDA-MB-231 cell line, and both extracts displayed significant anticancer activity. Hence, the findings in our study can be crucial in the area of herbal-based target-specific drug development against breast cancer.