The Effects of Apigenin-Biosynthesized Ultra-Small Platinum Nanoparticles on the Human Monocytic THP-1 Cell Line

Abstract

Generally, platinum nanoparticles (PtNPs) are considered non-toxic; however, toxicity depends on the size, dose, and physico-chemical properties of materials. Owing to unique physico-chemical properties, PtNPs have emerged as a material of interest for several biomedical applications, particularly therapeutics. The adverse effect of PtNPs on the human monocytic cell line (THP-1) is not well-established and remains elusive. Exposure to PtNPs may trigger oxidative stress and eventually lead to inflammation. To further understand the toxicological properties of PtNPs, we studied the effect of biologically synthesized ultra-small PtNPs on cytotoxicity, genotoxicity, and proinflammatory responses in the human monocytic cell line (THP-1). Our observations clearly indicated that PtNPs induce cytotoxicity in a dose-dependent manner by reducing cell viability and proliferation. The cytotoxicity of THP-1 cells correlated with an increase in the leakage of lactate dehydrogenase, generation of reactive oxygen species, and production of malondialdehyde, nitric oxide, and carbonylated proteins. The involvement of mitochondria in cytotoxicity and genotoxicity was confirmed by loss of mitochondrial membrane potential, lower ATP level, and upregulation of proapoptotic and downregulation of antiapoptotic genes. Decreases in the levels of antioxidants such as reduced glutathione (GSH), oxidized glutathione (GSH: GSSG), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and thioredoxin (TRX) were indicative of oxidative stress. Apoptosis was confirmed with the significant upregulation of key apoptosis-regulating genes. Oxidative DNA damage was confirmed by the increase in the levels of 8-oxodG and 8-oxoG and upregulation of DNA damage and repair genes. Finally, the proinflammatory responses to PtNPs was determined by assessing the levels of multiple cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1). All the cytokines were significantly upregulated in a dose-dependent manner. Collectively, these observations suggest that THP-1 cells were vulnerable to biologically synthesized ultra-small PtNPs.

Melatonin Enhances Palladium-Nanoparticle-Induced Cytotoxicity and Apoptosis in Human Lung Epithelial Adenocarcinoma Cells A549 and H1229

“…The same trend was observed in all other antioxidants, including TRX, CAT, SOD, GPx, and GST ( Figure 7B-F). Similarly, PtNPs also decreased antioxidant levels in several types of cancer cells, including SH-SY5Y cells [70], human monocytic THP-1 [71], and OS epithelial cells. In mammals, glutathione (GSH) is the dominant low-molecular-weight antioxidant.…”

“…Zhao et al [82] reported that titanium dioxide nanoparticles induced mitochondrial dynamic imbalance in HT22 cells, eventually causing mitochondrial dysfunctions and decreased level of ATP synthesis. Previous studies have shown that platinum nanoparticles decreased ATP synthesis in human THP-1 [71], prostate cancer cells [70], and osteosarcoma cells. Increased level of ROS reduced the oxidative capacity by altering the oxidative phosphorylation (OXPHOS), and decreased ATP production [83].…”

“…Finally, Alarifi et al [58] reported that PdNPs potentially induce apoptosis and oxidative DNA damage in A375 cells. Thus, PdNPs induce cytotoxicity and genotoxic effect in A549 cells, as other metallic NPs have been found to induce oxidative DNA damage in human ovarian cancer cells [22] as PtNPs have in human monocytic THP-1 cells [71]. The combination of PtNPs and doxorubicin caused significant oxidative DNA damage and accumulation of 8-OHdG and 8-OHG in osteosarcoma cancer cells.…”

A Comprehensive Review on the Synthesis, Characterization, and Biomedical Application of Platinum Nanoparticles

“…Synthesized NPs revealed potent anticancer activity against a human breast cancer cell line [100]. Similarly, biologically synthesized PtNPs exhibited potential cytotoxicity against various human cells such as human monocytic cells and human bone OS epithelial cells [101,102]. All these data provided strong evidence for the synthesis of PtNPs using natural products and its potential anticancer activity.…”

“…In vitro data suggest that PtNCP beads inhibited cell viability of HSC-3-M3 cells in a dose-dependent manner and induced cytotoxicity with increased leakage of lactate dehydrogenase [220]. Recently, Gurunathan et al [101] reported that apigenin functionalized PtNPs exhibited potential cytotoxicity, genotoxicity, and proinflammatory responses in human monocytic cell line (THP-1) by increasing the levels of lactate dehydrogenase, generation of ROS, and production of malondialdehyde, nitric oxide, and carbonylated proteins and also increased apoptosis and oxidative DNA damage. Finally, PtNPs increased the expression of various proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1).…”