Artocarpin Induces Apoptosis in Human Cutaneous Squamous Cell Carcinoma HSC-1 Cells and Its Cytotoxic Activity Is
Stephen Chu-Sung Hu1, Chi-Ling Lin2, Hui-Min Cheng3
1Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Abstract:
Artocarpin, a natural prenylated flavonoid, has been shown to have various biological properties. However, its effects on human cutaneous squamous cell carcinoma (SCC) have not been previously investigated. We set out to determine whether artocarpin has cytotoxic effects on SCC cells and whether its pharmacological activity is dependent on protein-nutrient concentration. Our results showed that treatment of HSC-1 cells (a human cutaneous SCC cell line) with artocarpin decreased cell viability and induced cell apoptosis by increasing caspase 3/7 activity. These effects were more pronounced at low fetal bovine serum (FBS) concentrations. Artocarpin induced an increase in the level of phospho-p38 and a decrease in the levels of phospho-ERK, phospho-JNK, phospho-Akt, phospho-mTOR, and phospho-S6K. High FBS concentrations in the culture media inhibited and delayed the uptake of artocarpin from the extracellular compartment (culture media) into the intracellular compartment, as determined by high performance liquid chromatography (HPLC) analysis. In conclusion, artocarpin induces apoptosis in HSC-1 cells through modulation of MAPK and Akt/mTOR pathways. Binding of artocarpin to proteins in the FBS may inhibit cellular uptake and reduce the cytotoxic activity of artocarpin on HSC-1 cells. Therefore, artocarpin may have potential use in the future as a form of treatment for cutaneous SCC.
Insights
Artocarpin, a natural compound, effectively reduced human squamous cell carcinoma (SCC) viability and induced apoptosis. Its efficacy was higher in low protein concentrations, suggesting potential for SCC treatment.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Artocarpin is a prenylated flavonoid with known biological activities.
- The effects of artocarpin on human cutaneous squamous cell carcinoma (SCC) remain uninvestigated.
Purpose of the Study:
- To determine the cytotoxic effects of artocarpin on human cutaneous SCC cells.
- To investigate the dependence of artocarpin's pharmacological activity on protein-nutrient concentration.
Main Methods:
- Treatment of HSC-1 cells (human cutaneous SCC cell line) with artocarpin.
- Assessment of cell viability, apoptosis (caspase 3/7 activity), and protein signaling pathways (MAPK, Akt/mTOR).
- High-performance liquid chromatography (HPLC) analysis to determine artocarpin uptake under varying fetal bovine serum (FBS) concentrations.
Main Results:
- Artocarpin decreased HSC-1 cell viability and induced apoptosis.
- Effects were more pronounced at low FBS concentrations.
- Artocarpin modulated MAPK and Akt/mTOR signaling pathways.
- High FBS concentrations inhibited artocarpin uptake into cells.
Conclusions:
- Artocarpin induces apoptosis in human cutaneous SCC cells via MAPK and Akt/mTOR pathway modulation.
- Protein binding in FBS may reduce artocarpin's cellular uptake and cytotoxic activity.
- Artocarpin shows potential as a future therapeutic agent for cutaneous SCC.
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