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Previously, we reported the immunostimulatory potential of the nanocomposite prepared from biopolymers (Pectin and Guar gum) and zinc oxide (Pec-gg-ZnO) on human peripheral-blood lymphocytes leading to enhanced anti-cancer immunity. The current study aims to describe the direct anti-cancer potential of Pec-gg-ZnO nanocomposite and the relevant mechanism of cell death induction in human lung carcinomas (A549). The cytotoxicity assay revealed the anti-cancer potential of Pec-ggZnO nanocomposite towards A549 cells, cervical adenocarcinoma (HeLa), and prostatic small cell carcinoma (PC-3). The IC50 values were 83.67 ± 0.10 μg/ml, 87.25 ± 0.03 μg/ml and 85.95 ± 0.03 μg/ml for A549, HeLa and PC-3 cells, respectively. The nanocomposite’s cancer cells’ killing capabilities were significantly higher than pectin and guar gum alone. Hemolysis assay revealed that synthesized Pecgg-ZnO nanocomposite is biocompatible at 2.5 mg/ml. S phase arrest with enhanced sub-G1 (apoptotic cells) population was examined in A549 cells treated with Pec-gg-ZnO nanocomposite. The nanocomposite caused apoptosis of target cells by inducing mitochondrial depolarisation, reactive oxygen species generation, caspase-3 and Poly (ADP-ribose) polymerase 1 (PARP1) activation resulting in DNA fragmentation. Collectively, the current data revealed that Pec-gg-ZnO nanocomposite is a novel polymer-based anti-cancer agent capable of inducing apoptotic pathways in cancer cells.

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