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Artemisinin: an alternative treatment for oral squamous cell carcinoma
Eiki Yamachika1, Temesgen Habte, Dolphine Oda
1Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Washington, Box 357134, Seattle, WA 98195-7134, USA.
Abstract:
Artemisinin (AR) is a widely used antimalarial drug. Recently, additional uses for AR as an anticancer drug were discovered. Using TUNEL, immunohistochemistry (IHS) markers and flow cytometry techniques, we evaluated the effect of AR and 5-FU on HPV 16 immortalized and transformed human gingival epithelial (IHGK) cells. The results of TUNEL showed that AR-treated IHGK cells consisted of 82% positive cells, while 5-FU-treated cells consisted of 18% positive cells. The IHS markers demonstrated positive staining with Bax p53, CD40 and CD40L in AR-treated cells and negative staining with Bcl-2. 5-FU-treated cells demonstrated a profile similar to AR but with less intensity. Cell cycle by flow cytometry results showed that only 5-FU-treated cells demonstrated a significant S-phase rate increase to 45%. In conclusion, our results indicate that AR is cytotoxic to transformed oral epithelial cells through apoptosis, while 5-FU is cytotoxic primarily through cell toxicity.
Insights
Artemisinin (AR) induces apoptosis in transformed oral epithelial cells, showing significant cytotoxicity. In contrast, 5-fluorouracil (5-FU) primarily causes cell toxicity with less apoptosis.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Artemisinin (AR), a known antimalarial, exhibits emerging anticancer properties.
- Human gingival epithelial (IHGK) cells, immortalized and transformed by HPV 16, serve as a model for oral cancer research.
Purpose of the Study:
- To investigate the cytotoxic effects of Artemisinin (AR) and 5-fluorouracil (5-FU) on HPV 16-transformed human gingival epithelial (IHGK) cells.
- To elucidate the mechanisms of cell death induced by AR and 5-FU in these cells.
Main Methods:
- Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect apoptosis.
- Immunohistochemistry (IHS) for apoptosis-related markers (Bax, p53, Bcl-2) and co-stimulatory molecules (CD40, CD40L).
- Flow cytometry to analyze cell cycle progression.
Main Results:
- TUNEL assay revealed 82% apoptosis in AR-treated IHGK cells versus 18% in 5-FU-treated cells.
- AR treatment upregulated pro-apoptotic markers (Bax, p53) and co-stimulatory molecules (CD40, CD40L) while downregulating anti-apoptotic Bcl-2.
- 5-FU induced similar but less intense marker changes and a significant increase in S-phase (45%), indicating cell cycle arrest.
Conclusions:
- Artemisinin (AR) demonstrates potent cytotoxicity against transformed oral epithelial cells, primarily through the induction of apoptosis.
- 5-fluorouracil (5-FU) exhibits cytotoxicity mainly via non-apoptotic cell toxicity mechanisms, including S-phase arrest.
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