Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism

Abstract

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose-dependently increase ROS levels in UM cells. At Cdots concentrations below 100 µg mL −1 , Cdot-induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 µg mL −1 , UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25-100 µg mL −1 activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS-producing nanoparticles in tumor imaging and therapy.

The Association of Aberrant Expression of FGF1 and mTOR-S6K1 in Colorectal Cancer

“…PI3K-Akt-mTOR is an important metabolic signaling pathway (27,28), which is aberrant expression in a variety of tumor cells (29)(30)(31)(32). Studies have shown that the abnormal activation of mTORC1 complex promotes the proliferation and migration ability of CRC cells (33)(34)(35).…”

Recent progress of carbon dots in targeted bioimaging and cancer therapy

“…The novel cellular energy metabolism performances indicated the potential applications of CDs in promising biomedicine for cancer therapy. In addition, Ding et al observed the novel dose-dependent cytotoxicity of CDs (Figure 19 F) 233 . In their work, researchers demonstrated the CDs-induced dose-dependent increase of ROS levels in Uveal melanoma (UM) cell metabolism, tumorigenicity of zebrafish and nude mouse xenograft model.…”

“…(g) Heatmap depicting changes in metabolite concentration between control and 50 µg mL-1 CDs-treated Mum2B cells (p < 0.05). Adapted with permission from 233 , copyright 2021 Wiley-VCH GmbH.…”

Monitoring Immunotherapy With Optical Molecular Imaging

“…As we discussed, ROS is closely related to tumor proliferation and death. [59] Excessive ROS may damage DNA structures, proteins and lipids by enhancing cell oxidative stress, and ultimately causes cell apoptosis and necrosis. [60] Several chemo- (ROS) in cancer cells.…”