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Chemotherapy side effects, medication resistance, and tumor metastasis impede the advancement of cancer treatments, resulting in a poor prognosis for cancer patients. In the last decade, nanoparticles (NPs) have emerged as a promising drug delivery system. Swertia chirayita has long been used as a treatment option to treat a variety of ailments. Zinc oxide nanoparticles (ZnO-NPs) were synthesized from ethanolic and methanolic extract of S. chirayita leaves. ZnO-NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron Microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD). Its anti-cancer activities were analyzed using cytotoxicity assays [MTT assay and acridine orange (AO) staining] and quantitative real-time PCR (qRT-PCR) using colorectal cancer (CRC) cells (HCT-116 and Caco-2) and control cells (HEK-293). The ZnO-NPs synthesized from the ethanolic extract of S. chirayita have an average size of 24.67 nm, whereas those from methanolic extract have an average size of 22.95 nm with a spherical shape. MTT assay showed NPs’ cytotoxic potential on cancer cells (HCT-116 and Caco-2) when compared to control cells (HEK-293). The IC50 values of ethanolic and methanolic extract ZnO-NPs for HCT-116, Caco-2, and HEK-293 were 34.356 ± 2.71 and 32.856 ± 2.99 μg/ml, 52.15 ± 8.23 and 63.1 ± 12.09 μg/ml, and 582.84 ± 5.26 and 615.35 ± 4.74 μg/ml, respectively. Acridine orange staining confirmed the ability of ZnO-NPs to induce apoptosis. qRT-PCR analysis revealed significantly enhanced expression of E-cadherin whereas a reduced expression of vimentin and CDK-1. Altogether, these results suggested anti-cancer properties of synthesized ZnO-NPs in CRC.

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