Silver nanoparticle functionalized by glutamine and conjugated with thiosemicarbazide induces apoptosis in colon cancer cell line.

The high mortality rate of colon cancer indicates the insufficient efficacy of current chemotherapy. Thus, the discussion on engineered metal nanoparticles in the treatment of the disease has been considered. In this study, silver nanoparticles were functionalized with glutamine and conjugated with thiosemiccarbazide. Then, anticancer mechanism of Ag@Gln-TSC NPs in a colon cancer cell line (SW480) was investigated. Characterizing Ag@Gln-TSC NPs by FT-IR, XRD, EDS-mapping, DLS, zeta potential, and SEM and TEM microscopy revealed that the Ag@Gln-TSC NPs were correctly synthesized, the particles were spherical, with surface charge of - 27.3 mV, high thermal stability and low agglomeration level. Using MTT assay we found that Ag@Gln-TSC NPs were significantly more toxic for colon cancer cells than normal fibroblast cells with IC50 of 88 and 186 µg/mL, respectively. Flow cytometry analysis showed that treating colon cancer cells with Ag@Gln-TSC NPs leads to a considerable increase in the frequency of apoptotic cells (85.9% of the cells) and increased cell cycle arrest at the S phase. Also, several apoptotic features, including hyperactivity of caspase-3 (5.15 folds), increased expression of CASP8 gene (3.8 folds), and apoptotic nuclear alterations were noticed in the nanoparticle treated cells. Furthermore, treating colon cancer cells with Ag@Gln-TSC NPs caused significant down-regulation of the HULC Lnc-RNA and PPFIA4 oncogene by 0.3 and 0.6 folds, respectively. Overall, this work showed that Ag@Gln-TSC NPs can effectively inhibit colon cancer cells through the activation of apoptotic pathways, a feature that can be considered more in studies in the field of colon cancer treatment.

Apoptosis induction in colon cancer cells (SW480) by BiFe2O4@Ag nanocomposite synthesized from Chlorella vulgaris extract and evaluation the expression of CASP8, BAX and BCL2 genes.

BACKGROUND: The use of nanomaterials in cancer diagnosis and treatment has received considerable interest. Preparation of nanoscale complex molecules could be considered to improve the efficacy and minimize toxicity of the product. This work aimed to biosynthesize BiFe2O4@Ag nanocomposite using the Chlorella vulgaris extract and its cytotoxic effect on colon cancer cell line. METHODS: The physicochemical properties of the bioengineered BiFe2O4 @Ag were investigated by Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FE-SEM), Zeta potential, Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FT-IR), Energy Dispersive X-ray Spectroscopy (EDX), Vibrating-sample Magnetometer (VSM) and X-ray Diffraction Analysis (XRD). The cytotoxic potential of BiFe2O4 @Ag was evaluated by MTT assay against SW480 colon cancer cell line. The expression levels of apoptotic genes including BAX, BCL2 and CASP8 were determined by Real-time PCR. The rate of apoptosis and necrosis of the cancer cells as well as the cell cycle analysis were evaluated by flow cytometry. RESULTS: Physicochemical assays indicated the nanoscale synthesis (10-70 nm) and functionalization of BiFe2O4 nanoparticles by Ag atoms. The VSM analysis revealed the magnetism of BiFe2O4 @Ag nanocomposite. According to the MTT assay, colon cancer cells (SW480) were considerably more sensitive to BiFe2O4 @Ag nanocomposite than normal cells. Apoptotic cell percentage increased from 1.93% to 73.66%, after exposure to the nanocomposite. Cell cycle analysis confirmed an increase in the number of the cells in subG1 and G0/G1 phases among nanocomposite treated cells. Moreover, treating the colon cancer cells with BiFe2O4 @Ag caused an increase in the expression of CASP8, BAX, and BCL2 genes by 3.1, 2.6, and 1.2 folds, respectively. Moreover, activity of Caspase-3 protein increased by 2.4 folds and apoptotic morphological changes appeared which confirms that exposure to the nanocomposite induces extrinsic pathway of apoptosis in colon cancer cells. CONCLUSION: The considerable anticancer potential of the synthesized BiFe2O4 @Ag nanocomposite seems to be related to the induction of oxidative stress which leads to inhibit cell cycle progression and cell proliferation. This study reveals that the BiFe2O4 @Ag is a potent compound to be used in biomedical fields.

Trigger of apoptosis in adenocarcinoma gastric cell line (AGS) by a complex of thiosemicarbazone and copper nanoparticles.

BACKGROUND: Seeking novel anticancer agents with minimal side effects against gastric cancer is vitally important. Copper, as an important trace element, takes roles in different physiologic pathways. Also, there is a higher demand for copper in cancer cells than normal ones. Copper complexes containing a therapeutic ligand could be promising candidates for gastric cancer chemotherapy. METHODS AND RESULTS: In this work, copper oxide nanoparticles were synthesized, functionalized with glutamic acid (CuO@Glu) and conjugated with thiosemicarbazone (CuO@Glu/TSC NPs). The NPs were characterized and their antiproliferative potential against AGS cancer cells was investigated using MTT, flow cytometry, Hoechst staining, and caspase 3 activation assays. The FT-IR results showed the proper binding of TSC to CuO@Glu NPs and crystallinity of the prepared NPs was confirmed by the XRD pattern. The EDX analysis confirmed the presence of Cu, N, C, O, and S elements and lack of impurities. The Hydrodynamic size and zeta potential of the CuO@Glu/TSC NPs were 168 nm and 27.5 mV, respectively. The NPs had spherical shape and were in a size range of 10 to 60 nm in diameter. This work revealed that CuO@Glu/TSC NPs efficiently inhibited the proliferation of AGS cells with significantly lower IC50 value (203 µg/mL) than normal HEK293 cells (IC50 = 435 µg/mL). Flow cytometry and Hoechst staining obviously revealed apoptosis induction among CuO@Glu/TSC treated cells, and caspase-3 activity significantly increased by 1.4 folds. CONCLUSIONS: This study introduced CuO@Glu/TSC as an efficient anticancer against gastric cancer cells with lower toxicity toward normal cells which could be employed for cancer treatment after further studies.