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Ginseng-based carbon dots inhibit the growth of squamous cancer cells by increasing ferroptosis
Zilin Wang1,2, Jing Han1,2, Zhiyong Guo1,2,3
1Department 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.
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.
Insights
Ginseng-based carbon dots (GCDs) show anticancer effects by inducing ferroptosis, inhibiting cancer cell growth and invasion in vitro and in vivo. These findings highlight GCDs as a potential therapeutic agent for cancer treatment.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Ginseng exhibits potential in cancer treatment.
- Ginseng-based carbon dots (GCDs) may possess anticancer properties.
- This study explores GCDs' effects on cancer cells and their mechanisms.
Purpose of the Study:
- Synthesize and characterize GCDs.
- Evaluate GCDs' impact on cancer cell growth, invasion, and migration.
- Investigate the molecular mechanisms underlying GCDs' anticancer effects, including ferroptosis.
Main Methods:
- GCDs were synthesized, purified, and characterized using electron microscopy.
- Cancer cell lines (Cal-27, SCC-25, SCC-7, HaCaT) were treated with GCDs to assess growth, invasiveness, and wound healing.
- Transcriptomics, western blot, and immunohistochemistry were employed to analyze molecular changes. In vivo studies involved tumor-bearing mice treated with GCDs.
Main Results:
- GCDs (approx. 4 nm) inhibited cancer cell growth and non-cancerous cell growth at specific concentrations.
- Transcriptomic analysis revealed alterations in oxidative phosphorylation and ferroptosis pathways.
- GCDs induced cancer cell ferroptosis (decreased GPX-4, increased COX-2), reduced invasion/migration, and suppressed tumor growth in mice with increased CD4+ T cell infiltration.
Conclusions:
- GCDs demonstrate significant anticancer properties.
- GCDs induce ferroptosis, leading to cancer cell growth inhibition.
- GCDs show promise for in vitro and in vivo cancer therapy with minimal toxicity.
