Computational and experimental pharmacology mediated assessment of bioactives from Laportea interrupta (L.) Chew. leaf extract against luminal A breast cancer

Breast cancer is a heterogeneous malignancy characterized by diverse pathological and molecular profiles, which are assessed and predicted using a variety of immunohistochemical (IHC) markers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67.The diagnostic and prognostic evaluation of breast cancer is further nuanced by factors such as tumour size, histological grade, and lymph node involvement.Notably, ER-positive or luminal tumors, which constitute over two-thirds of breast cancer cases, exhibit considerable heterogeneity in their histological features, gene expression patterns, and mutational landscapes, resulting in a broad spectrum of clinical outcomes and therapeutic responses.In this context, the study explored the therapeutic potential of the ethnomedicinal plant Laportea interrupta (L.) Chew. in treating luminal A breast cancer.This plant, known for its antibacterial, thrombolytic, antioxidant, membrane-stabilizing, cytoprotective, and nephroprotective properties, was subjected to in vitro cytotoxicity assays and systems biology analyses.Gas chromatography-mass spectrometry (GC-MS) analysed the ethanolic leaf extract to identify key bioactive compounds.Among the identified compounds, 2-[4-methyl-6-(2,6,6-trimethylcyclohex-1enyl)hexa-1,3,5-trienyl]cyclohex-1-en-1-carboxaldehyde exhibited notable binding affinities, with docking scores of -6.611 kcal/mol, -4.744 kcal/mol, and -3.950 kcal/mol for PR (PDB ID: 4OAR), ER (PDB ID: 3ERT), and epidermal growth factor receptor (EGFR, PDB ID: 2J6M), respectively.In vitro assays demonstrated that the ethanolic extract had IC 50 values of 80.53 0.428 g/ml against MCF-7 cells and 107.51 0.558 g/ml against T-47D cells, both of which are luminal A subtypes.For comparison, doxorubicin exhibited IC 50 values of 26.07 15.70 g/ml for MCF-7 cells and 35.74 0.65 g/ml for T-47D cells.Although, the ethanolic extract's cytotoxic efficacy was lower than that of doxorubicin, it demonstrates notable potential as an alternative therapeutic agent for luminal A breast cancer.Further, in vivo studies are warranted to substantiate its efficacy and safety profile.Future research should aim at comprehensive in vivo evaluations and the development of strategies to enhance therapeutic efficacy and overcome drug resistance in challenging cancer subtypes.