Eco-Friendly Influence of Gamma-Irradiation on (Acrylamide/Carbon Disulfide) as a Potential Anticancer Agent Induced Apoptotic Cell Death in Pancreatic Carcinoma Cell Line

Abstract

Polyacrylamide (PAAm) was made from acrylamide (AAm), polycarbondisulfide (PCS₂) from carbon disulfide (CS₂), and their copolymer P(AAm/CS₂) at a fixed equal ratio using gamma irradiation. The polymers were characterized using Fourier-transform infrared spectroscopy (FTIR), CHNS/O elemental microanalysis, x-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and gel permeation chromatography (GPC). The results demonstrated the effective synthesis of PAAm, PCS₂, and P(AAm/CS₂), with the copolymer having an average molecular weight of 187,673 Da. The produced polymers were tested for their cytotoxic and pro-apoptotic effects on human pancreatic carcinoma (PANC-1) cells in light of the urgent need for efficient treatments against this aggressive cancer with a poor prognosis. With half-maximal inhibitory concentrations (IC₅₀) of > 500 μg/mL for PAAm, 156 μg/mL for PCS₂, and 99.2 μg/mL for P(AAm/CS₂), the copolymer demonstrated superior cytotoxic potential. Flow cytometric analysis provided additional support for these findings. Treatment with 125 μg/mL of PAAm resulted in 4.8% early and 13.3% late apoptosis, whereas PCS₂ at the same concentration caused 30.8% early and 18.5% late apoptosis. Notably, 125 μg/mL of P(AAm/CS₂) caused a significant increase in apoptosis, resulting in 39.3% of early apoptotic cell populations and 28.6% of late apoptotic cell populations. According to gene expression analysis, P53, Caspase-3, Caspase-7, and Bax genes were upregulated and Bcl-2 was downregulated after treatment with 125 μg/mL of PCS₂ or P(AAm/CS₂). However, PAAm had no significant impact on these apoptotic markers. In comparison to untreated PANC-1 cells, P(AAm/CS₂) showed the strongest response, resulting in significant (p ≤ 0.05) increases in P53 (4.4-fold), Caspase-3 (2.9-fold), Caspase-7 (8.3-fold), and Bax (5.5-fold) expression levels, while Bcl-2 expression was significantly reduced (0.09-fold). In conclusion, the produced copolymer P(AAm/CS₂) exhibits a strong anticancer effect on pancreatic carcinoma cells by inducing apoptosis, thereby supporting its potential as a promising polymer-based therapeutic agent.