Synthesize of Bi2O3/Gln-TSC nanoparticles and evaluation of their toxicity on prostate cancer cells and expression of CASP8, BAX, and Bcl-2 genes

Bi2O3/Gln-TSC 纳米粒子的合成及其对前列腺癌细胞的毒性和 CASP8、BAX 和 Bcl-2 基因表达的评估

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作者:Asal Moradi, Mohammadreza Abdihaji, Sara Barari Kouchaksaraie, Tabarek Abdulrazaq Alkinani, Aida Mahmoudi, Arash Davoudi, William Dashtmiani, Somayeh Mikaeili Ghezeljeh, Shahrzad Aghajani, Reza Ghasemian, Somayeh Maghsoomi Taramsari, Amitis Majlesi, Zahra Mahdavi Niyaki, Ali Salehzadeh

Abstract

Due to the high prevalence and considerable increase of prostate cancer, finding novel therapeutic compounds for the treatment of prostatic cancer has been the goal of many researches. In this study, we aimed to fabricate the Bismuth oxide (Bi2O3) NPs, functionalized with glutamine (Gln) and conjugated with Thiosemicarbazide (TSC). Then, the anticancer mechanism of the synthesized NPs was investigated using the cellular and molecular tests including MTT assay, Flow cytometry, Caspase-3 activity assay, Hoechst staining and Real Time PCR. The FT-IR and XRD assays confirmed the identity of the synthesized Bi2O3/Gln-TSC NPs. The size range of the synthesized spherical particles was 10-60 nm and the zeta potential was - 23.8 mV. The purity of the NPs was confirmed by EDX-mapping analysis. The Bi2O3/Gln-TSC was considerably more toxic for prostate cancer cells than normal human cells and the IC50 was calculated 35.4 and 305 µg/mL, respectively. The exposure to the NPs significantly increased the frequency of apoptotic cells from 4.7 to 75.3%. Moreover, the expression of the CASP8, BAX, and Bcl-2 genes after exposure to the NPs increased by 2.8, 2.3, and 1.39 folds. Treating the cancer cells with Bi2O3/Gln-TSC increased the activity of the Caspase-3 protein and apoptotic morphological features were observed by Hoechst staining in the treated cells. This work showed that Bi2O3/Gln-TSC has considerable cytotoxicity for prostate cancer cells and could inducing both intrinsic and extrinsic pathways of apoptosis.

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