Biologically synthesized black ginger-selenium nanoparticle induces apoptosis and autophagy of AGS gastric cancer cells by suppressing the PI3K/Akt/mTOR signaling pathway

Abstract

Background Despite being a promising strategy, current chemotherapy for gastric cancer (GC) is limited due to adverse side effects and poor survival rates. Therefore, new drug-delivery platforms with good biocompatibility are needed. Recent studies have shown that nanoparticle-based drug delivery can be safe, eco-friendly, and nontoxic making them attractive candidates. Here, we develop a novel selenium-nanoparticle based drug-delivery agent for cancer treatment from plant extracts and selenium salts. Results Selenium cations were reduced to selenium nanoparticles using Kaempferia parviflora (black ginger) root extract and named KP-SeNP. Transmission electron microscopy, selected area electron diffraction, X-ray diffraction, energy dispersive X-ray, dynamic light scattering, and Fourier-transform infrared spectrum were utilized to confirm the physicochemical features of the nanoparticles. The KP-SeNPs showed significant cytotoxicity in human gastric adenocarcinoma cell (AGS cells) but not in normal cells. We determined that the intracellular signaling pathway mechanisms associated with the anticancer effects of KP-SeNPs involve the upregulation of intrinsic apoptotic signaling markers, such as B-cell lymphoma 2, Bcl-associated X protein, and caspase 3 in AGS cells. KP-SeNPs also caused autophagy of AGS by increasing the autophagic flux-marker protein, LC3B-II, whilst inhibiting autophagic cargo protein, p62. Additionally, phosphorylation of PI3K/Akt/mTOR pathway markers and downstream targets was decreased in KP-SeNP-treated AGS cells. AGS-cell xenograft model results further validated our in vitro findings, showing that KP-SeNPs are biologically safe and exert anticancer effects via autophagy and apoptosis. Conclusions These results show that KP-SeNPs treatment of AGS cells induces apoptosis and autophagic cell death through the PI3K/Akt/mTOR pathway, suppressing GC progression. Thus, our research strongly suggests that KP-SeNPs could act as a novel potential therapeutic agent for GC. Graphical Abstract

JI017 Induces Cell Autophagy and Apoptosis via Elevated Levels of Reactive Oxygen Species in Human Lung Cancer Cells

“…JI017 treatment decreased the levels of PI3K, AKT, and mTOR in H460 and H1299 cells (Figure 3A). The inhibition of mTOR is known to increase autophagy signaling [49]. To investigate whether JI017 induces autophagy, Western blot analysis was used, and it was confirmed in H460 and H1299 cells.…”

Ferritinophagy Mediated by Oxidative Stress-Driven Mitochondrial Damage Is Involved in the Polystyrene Nanoparticles-Induced Ferroptosis of Lung Injury

“…Most of the previous studies on the pulmonary toxicity of nanoparticle focused on apoptosis and pyroptosis. 30,31 However, nanoparticles always cause mixed forms of cell death. 32 Knowing the role of ferroptosis in nanoparticle-induced cell death may contribute to an in-depth understanding of nanoparticle respiratory toxicity and the discovery of potential medical applications.…”

Trends and recent progresses of selenium nanoparticles as novel autophagy regulators for therapeutic development

“…These works would further explain whether these potential pathways are critical for the control of Se NPs induced autophagy. Secondly, the relations between autophagy and apoptosis are also needed to be further investigated in Se NPs induced autophagy, as most of the results indicated that Se NPs could both induce autophagy and apoptosis ( 63 , 67 , 73 ).…”

“…Thirdly, the toxicity issue of Se NPs should be considered as one of the most important issues for the further application of Se NPs. Although some works have indicated that Se NPs could inhibit cancer cells selectively without significant inhibition effects on normal cells ( 63 , 89 ), the detailed mechanisms for these selectivity are still unknown. And there are still few studies that specifically focus on the systemic toxicity of long-term Se NPs treatment in vivo .…”

“…Thus, the development of novel strategies, such as drug-delivery platforms with good biocompatibility that could enhance chemotherapy efficiency and reduce the side effects against cancer, remain a challenge. Wang et al ( 63 ) developed a novel selenium-nanoparticle based drug-delivery agent for cancer treatment from Kaempferia parviflora (black ginger) root extract and selenium salts. The obtained KP-Se NPs showed significant cytotoxicity in human gastric adenocarcinoma cells (AGS cells), but showed no significant cytotoxicity in normal cells.…”