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Phytochemical Characterization of Tupistra nutans Inflorescence and its Cytostatic and Anti-Migratory Effect in
Bibhushan Dhungyal1, Bhavana Ramachandran2, Brintha S2
1Department of Physiology, Sikkim Manipal Institute of Medical Sciences (SMIMS), Gangtok, Sikkim, India. bibhushan.d@smims.smu.edu.in.
Abstract:
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.
Insights
This study explores the anti-tumorigenic effects of Tupistra nutans (TN) on triple-negative breast cancer (TNBC). TN selectively reduces TNBC cell viability and migration without causing genotoxicity, suggesting potential as a novel cancer therapy.
Area of Science:
- Phytochemistry
- Cancer Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
- Conventional chemotherapy for TNBC can lead to drug resistance and severe toxicity.
- Tupistra nutans (TN), a plant from the Northeastern Himalayas, is explored for its therapeutic potential.
Purpose of the Study:
- To investigate the anti-tumorigenic effects of Tupistra nutans (TN) on triple-negative breast cancer (TNBC).
- To determine the phytochemical composition of TN and predict potential therapeutic compounds.
- To evaluate the selective cytotoxicity, anti-migratory effects, and genotoxicity of TN on TNBC cells.
Main Methods:
- ICP-MS and GC-MS analysis for phytochemical profiling of TN.
- In vitro assays using TNBC cell lines (MDA-MB-231, HCC1937) and normal HEK-293T cells.
- Immunofluorescence for γ-H2A.X and neutral comet assay to assess genotoxicity.
Main Results:
- TN exhibited selective cytotoxicity against TNBC cells with IC₅₀ values significantly lower than in normal cells.
- TN demonstrated anti-migratory effects in MDA-MB-231 cells.
- TN did not induce genotoxicity but upregulated NBR2 and downregulated BRCA1, suggesting metabolic stress signaling.
Conclusions:
- Tupistra nutans possesses selective cytostatic effects against triple-negative breast cancer cells.
- TN shows potential as a non-genotoxic agent with anti-migratory properties for TNBC treatment.
- Further research is needed to elucidate TN's mechanisms and its role in combination therapies.
