Ginseng-based carbon dots inhibit the growth of squamous cancer cells by increasing ferroptosis

Zilin Wang; Jing Han; Zhiyong Guo; Hao Wu; Yige Liu; Wenying Wang; Chenping Zhang; Jiannan Liu

doi:10.3389/fonc.2023.1097692

Ginseng-based carbon dots inhibit the growth of squamous cancer cells by increasing ferroptosis

Front Oncol. 2023 Mar 10:13:1097692. doi: 10.3389/fonc.2023.1097692. eCollection 2023.

Authors

Zilin Wang^{1

2}, Jing Han^{1

2}, Zhiyong Guo^{1

2

3}, Hao Wu^{1

2

4}, Yige Liu^{1

2

3}, Wenying Wang², Chenping Zhang^{1

2}, Jiannan Liu^{1

2}

Affiliations

¹ Department of Oral Maxillofacial - Head & Neck Oncology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, China.
² College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
³ Shanghai Key Laboratory of Tissue Engineering Research, Shanghai, China.
⁴ School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.

Abstract

Background: Recent studies indicated that Ginseng potentiate cancer treatments. Ginseng-based carbon dots (GCDs) might possess properties to kill cancer cells and inhibit malignant tumor development and invasion. This study aimed to prepare GCDs, examine their effects on cancer cell growth and invasion, and explore the mechanisms involved.

Methods: GCDs were synthesized, purified, and characterized. Cells were cultured with GCDs and were tested for growth, invasiveness, and wound healing. RNA was extracted for transcriptomics analysis. Protein expression was evaluated using western blot and immunohistochemistry. Mice were injected with cancer cells and treated with PBS or GCDs. Tumor volume was evaluated.

Results: GCDs were successfully synthesized and purified. The solution was yellow under sunlight and fluorescent blue under ultraviolet light. Electron microscopy showed GCDs with a uniform shape without apparent aggregation and an average diameter of about 4 nm. GCDs inhibited Cal-27, SCC-25, and SCC-7 cancer cell growth at concentrations of >250-300 μg/mL, while GCDs inhibited the non-cancerous HaCaT cells at concentrations >400 μg/mL. Immunofluorescence showed that GCDs could enter the cells. Transcriptomics revealed 552 downregulated mRNAs and 338 upregulated ones, including mRNAs involved in the oxidative phosphorylation and ferroptosis pathways. GCDs induced the ferroptosis of cancer cells, as shown by decreased GPX-4 and increased COX-2. GCDs decreased cell invasion and migration. In vivo, GCDs decreased tumor growth without apparent organ toxicity and promoted CD4⁺ T cell infiltration in the tumor.

Conclusion: GCDs appear to possess anticancer properties by increasing ferroptosis, resulting in cancer cell growth inhibition in vitro and in vivo.

Keywords: carbon dots; ferroptosis; ginseng; nanomaterials; neoplasm invasiveness; squamous cancer.

Grants and funding

This study was supported by Natural Science Fund of China (82170923, 81901049), Clinical Research Plan of SHDC (SHDC2020CR3008A), and China Postdoctoral Science Foundation (2021TQ0206, 2021M690105).