Phytochemical Characterization of Tupistra nutans Inflorescence and its Cytostatic and Anti-Migratory Effect in Breast Cancer Cells.

Breast cancer is one of the leading causes of cancer related mortality in women. Triple negative breast cancer (TNBC), characterized by the absence of ER, PR and HER2 receptors, is particularly challenging to target owing to its highly aggressive nature. Conventional chemotherapeutic agents cause drug resistance, cancer remission and high toxicity even to normal cells. Tupistra nutans (TN) is a flowering plant of the Asparagaceae family and is widely consumed in the Northeastern Himalayan regions. This is the first study exploring the anti-tumorigenic effect of TN on triple-negative breast cancer (TNBC) subtype. We perform ICP-MS and GC-MS analysis to provide comprehensive insights into the phytochemical composition of TN. Using the PASS online tool, we predict that compounds identified in GC-MS such as diosgenin, rhodopin and 1,2-cyclopentanedione, act as apoptosis agonist, MMP9 inhibitor and myc inhibitor respectively. In vitro studies demonstrated IC₅₀ values of 15.2, 28.2, and 70.1 µg/mL at 48 hours in the TNBC cells MDA-MB-231 and HCC1937 and in the normal epithelial-like HEK-293T cell line, respectively, suggesting selective cytotoxicity toward cancer cells. TN shows an anti-migratory effect in MDA-MB-231 cells and was not found to cause apoptosis. Through immunofluorescence for γ-H2A.X, and neutral comet assay we also demonstrate that TN does not induce genotoxicity, rather it upregulates NBR2, indicating possible metabolic stress signalling, and downregulates BRCA1 transcript. TN likely has a cytostatic effect selectively in TNBC cells, indicating functional suppression of tumorigenic properties. Further studies are required to elucidate the underlying mechanisms, and its potential use in combinatorial therapies.