Eco-Friendly Influence of Gamma-Irradiation on (Acrylamide/Carbon Disulfide) as a Potential Anticancer Agent Induced
Sanna R Mahdy1, Salwa A Khalil1, Ahmed Awadallah-F2
1Radiation Chemistry Department, National Centre for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
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.
