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Seneviratne, N. N.

Publications and source records attributed to Seneviratne, N. N..

2 recordsLinked to original sources

Anti-proliferative and Apoptosis Inducing Effect of Thymoquinone in Human Teratocarcinomal (NTERA-2) Cancer Stem-Like Cells

Cancer stem cells (CSCs) are key drivers of tumor progression, therapeutic resistance and recurrence. Nigella sativa, a medicinal plant widely used in traditional medicine, has gained significant importance due to its diverse pharmacological properties. Thymoquinone (TQ), a biologically known active compound isolated from N.sativa, has demonstrated anticancer properties in various cancers. However, its effect on CSC-like cells has not been fully elucidated. In the present study, the anti-proliferative and apoptosis inducing properties of TQ was evaluated on human embryonal carcinoma cells (NTERA-2, cancer stem cell like model) and human peripheral blood mononuclear cells (PBMCs) in vitro. Antiproliferative effects of TQ on NTERA-2 cells and PBMCs were evaluated using the Sulforhodamine B (SRB) and WST-1 assays, respectively. The effect of TQ was further evaluated using colony formation assay, cell migration assay, fluorescence microscopy and quantification of caspase 3/7 activities. Oxidative stress markers (reactive oxygen species [ROS]) were also determined in NTERA-2 cells treated with TQ. Thymoquinone revealed promising dose- and time-dependent antiproliferative effects (half-maximal inhibitory concentration [IC50] 1.282, 1.167, and 0.984 g/mL at 24, 48, and 72 h post-treatment) in NTERA-2 cells while exerting a minimal cytotoxic effect in PBMCs. Apoptosis related morphological changes, and increased Caspase 3/7 activities confirmed the pro-apoptotic effects of TQ. Further, NTERA-2 cells treated with TQ expressed a significant increase (P < 0.001) in intracellular ROS activity. Overall results confirm that TQ exerts anti-proliferative and apoptotic effects in a dose- and time-dependent manner. Therefore, TQ can be considered as a potent drug lead for chemotherapy and radiotherapy resistant cancer stem cells.

pharmacology and toxicology↗

In vitro anti-cancer properties of a commercially available polyherbal nutraceutical (Vernolac) capsule on cancer stem cell-like (NTERA-2 cl.D1) cells.

Vernolac is a commercially available polyherbal nutraceutical formulation comprising Vernonia zeylanica aerial parts, Nigella sativa seeds, Hemidesmus indica roots, Smilax glabra rhizome, and Leucas zeylanica aerial parts. Previous studies have demonstrated anti-cancer activities of phytochemicals derived from these individual plant components. However, the anti-cancer properties of the supercritical CO2 extract of Vernolac remain unexplored against cancer stem-like cell populations. The current study is focused on the anti-cancer potential of Vernolac extract on NTERA-2 cl.D1 cancer stem-like model, a human embryonal carcinoma-derived pluripotent cell line. Gas Chromatography-Mass Spectrometry (GC-MS) was performed for phytochemical analysis. Several in vitro assays evaluated the anti-cancer properties of the Vernolac extract. Cytotoxicity was assessed using the Sulforhodamine B assay, and apoptosis induction was determined by Acridine Orange/Ethidium Bromide staining and the caspase 3/7 activity assay. Scratch assay was used to evaluate cell migration, and Reverse Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR) was performed to analyze the expression levels of apoptosis-related genes (TP53, BIRC5) and the autophagy-related gene mTOR. Further, the free-radical scavenging activity of Vernolac extract was assessed using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. The reactive oxygen species levels in NTERA-2 cl.D1 cells were quantified using the nitroblue tetrazolium assay. GC-MS analysis revealed 20 phytochemical constituents in the supercritical CO2 extract. In vitro assay results demonstrated that Vernolac extract exhibits significant anti-proliferative activity in NTERA-2 cl.D1 cells, with an IC50 of 41.12 {micro}g/mL at 48 h, while exerting minimal effects on non-cancerous MCF-10A cells (IC50 > 1000 g/mL). Fluorescence microscopy and caspase 3/7 assay showed that Vernolac extract leads to early apoptosis in NTERA-2 cl.D1 cells. RT-qPCR revealed the upregulation of tumor suppressor protein P53 while downregulating BIRC5 and mTOR. Additionally, Vernolac extract inhibited the migration rate of NTERA-2 cl.D1 cells and elevated intracellular reactive oxygen species levels. These findings suggest that the supercritical CO2 extract of Vernolac exerts potent anticancer properties against NTERA-2 cl.D1 cancer stem-like model, highlighting its therapeutic potential for targeting cancer stem cells.

pharmacology and toxicology↗