Enhanced anticancer activity of nanoemulsified cardamom extract via modulation of apoptosis- and lncRNA-associated pathways in colorectal cancer cells

Colorectal cancer is a common, deadly disease, highlighting the need for safe and effective treatments. This study compared the anticancer effects of crude and nanoemulsified <i>Elettaria cardamomum</i> (cardamom) extract on HCT-116 colorectal cancer cells. Both the crude extract and nanoemulsion were prepared, and the nanoemulsion was characterized using transmission electron microscopy and dynamic light scattering. In an <i>in vitro</i> study, cell viability was measured by MTT assay, apoptosis by Annexin V/PI staining, and migration by scratch assay. The expression of genes related to apoptosis, migration, and angiogenesis, as well as lncRNAs MALAT1, NEAT1, and GAS5, was analyzed using real-time PCR. Physicochemical analysis showed spherical nanoemulsion particles with two size populations in a multimodal distribution. The IC₅₀ was found to be 279 μg/mL for crude extract and 54.36 μg/mL for the nanoemulsion. Our molecular findings showed that the cardamom nanoemulsion exerted significantly stronger anticancer effects than the crude extract, including a greater decrease in cell viability, increased apoptosis, and more effective migration inhibition. Gene expression analysis showed that the nanoemulsion upregulated BAX and GAS5 while downregulating BCL2, MMP2, MMP9, HIF1A, VEGFA, MALAT1, and NEAT1. These expression changes were particularly pronounced at early time points compared to the crude extract. Bioinformatic analyses identified correlations between these lncRNAs and crucial genes involved in cell survival, migration, and angiogenesis, emphasizing possible lncRNA-miRNA-mRNA regulatory axes. The cardamom nanoemulsion demonstrates enhanced anticancer activity relative to the crude extract and could represent a novel therapeutic approach for colorectal cancer by modulating lncRNAs and related molecular pathways.