Cytotoxicity effect of nickel hydroxide nanoparticles functionalized by glutamine and conjugated by thiosemicarbazide on human lung cancer cell line (A549) and evaluation of bax and bcl-2 genes expression

• Published in: Gene reports Vol. 29; p. 101700
• Main Authors: Dehkaei, Artadokht Aghaeipour, Khalatbari, Kimia, Emamifar, Alireza, Taramsari, Somayeh Maghsoomi, Balkhi, Sahar, Ghezeljeh, Somayeh Mikaeili, Gorji, Selena, Gholipoor, Sevda, Noveiri, Mahboubeh Jahani Sayyad, Hedayati, Mohammad, Salehzadeh, Ali
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.12.2022
• Subjects: A549 cells; Apoptosis; Caspase-3; Glutamine; NP; DRS; A549 cells; Gln; TSCs; DLS; XRD; Caspase-3; EDS; FTIR; SEM; TEM; Apoptosis; Glutamine
• ISSN: 2452-0144; 2452-0144
• DOI: 10.1016/j.genrep.2022.101700

Lung cancer is the second leading cause of cancer-associated death, worldwide and current therapeutic approaches have low efficiency in treating metastatic lung cancers. Thiosemicarbazones (TSCs) in the free and complexed forms showed promising anticancer potential. This study aimed to fabricate nickel oxide nanoparticles conjugated with TSC and characterize their anticancer mechanism. Ni(OH)2 nanoparticles were conjugated with TSC through glutamine (Gln) linker. The physicochemical feature of the nanoparticle (NP) was characterized and their cytotoxicity mechanism was investigated by the cellular and molecular assays. The FT-IR and XRD analyses confirmed the fabrication of the nanoparticle and the purity of the particles was confirmed by EDX-mapping. The particles were spherical within a size range of 23–55 nm. The hydrodynamic size and zeta potential of the nanocomposite were 265 nm and −45 mV, respectively. Ni(OH)2@Gln-TSC showed considerably higher toxicity for A549 lung cancer cells than HEK-293 human normal cells with IC50 of 160 and 310 μg/mL, respectively. Treating the A549 cells with Ni(OH)2@Gln-TSC caused apoptosis induction in 79.5 % of the cells and 66.6 % of the cells were arrested at the sub-G1 phase. Also, the expression of the bax gene was increased by 2.8 folds following treating with the NP, while the bcl-2 gene was attenuated by 0.85 folds. Furthermore, the activity of Caspase-3 was increased in the Ni(OH)2@Gln-TSC treated cells, and nuclear damages including chromatin condensation and fragmentation were observed. This study showed that the Ni(OH)2@Gln-TSC NP has considerable cytotoxicity for lung cancer cells through the activation of cell apoptosis pathways. [Display omitted] •Treating the A549 cells with Ni(OH)2@Gln-TSC NP caused apoptosis induction in 79.5% of the cells.•Expression of the bax gene was increased by 2.8 fold, while the bcl-2 gene was attenuated by 0.85 fold.•Activity of Caspase-3 was increased in the Ni(OH)2@Gln-TSC treated cells.