Anticancer activity of zinc-nickel nanocomposite in lung cancer PC14 cells via modulation of apoptosis and P13K/mTOR pathway

Abstract

Advanced innovations for combating variants of aggressive cancer and overcoming drug resistance are desired. In cancer treatment, nanoparticles (NPs) have the capacity to specifically and compellingly activate apoptosis of cancer cells. There is also a pressing need to develop innovative anti-cancer therapeutics, and recent research suggests that ZnO nanoparticles hold great potential.The current exploration was designed to fabricate the zinc-nickel nanomaterial (Zn-Ni NPs) and examine its in vitro anticancer effects on lung cancer cell. In ultraviolet–visible spectroscopy (UV–Vis), the bands at the wavelengths of 219, 265, 397, and 458 nm are related to the surface plasmon resonance of the synthetic Zn-Ni NPs. In fourier transform-infrared spectroscopy (FT-IR), the peaks of 449, 618, 659, 662, and 693 can be assigned to Zn-O or Ni-O bonds. The cytotoxicity of the Zn-Ni NPs (1 to 1000 µg/mL) were studied by the MTT assay and the IC50 dose for Zn-Ni NPs were found at 77 µg/mL. The different fluorescent staining assays such as Dichloro-dihydro-fluorescein diacetate, Rhodamine-123, and dual staining were performed to investigate the influence of Zn-Ni NPs on the apoptosis, matrix metalloproteinase status, and reactive oxygen species accumulation in the PC14 cells. The status of inflammatory markers such as IL-6, COX-2, TNF-α, and NF-κB in the PC14 cells were studied. The increased dosage of Zn-Ni NPs were effective repressed the growth of PC14 cells. The PC14 cells treated with Zn-Ni NPs revealed a significantly fewer proliferating cells and more apoptotic cells when compared with control. The Zn-Ni NPs also inhibited the phosphorylation of mTOR and Akt, reducing tumor volume and weight. PC14 cells phosphorylated mTOR, cyclin D1, Akt, and PI3K in response to Zn-Ni NPs. The findings were revealed that the fabricated Zn-Ni NPs considerably increased the ROS accumulation and apoptosis in the PC14 cells. Zn-Ni NPs also enhanced mitochondrial apoptosis through Bcl-2 protein-dependent signaling. In conclusion, Zn-Ni NPs might be promising candidate for lung cancer treatment.