Artemisinin induces apoptosis in human cancer cells
Narendra P Singh1, Henry C Lai
1Department of Bioengineering, University of Washington, Seattle, Washington 98195-7962, USA. Narendra@u.washington.edu
Background:
Artemisinin is a chemical compound extracted from the wormwood plant, Artemisia annua L. It has been shown to selectively kill cancer cells in vitro and retard the growth of implanted fibrosarcoma tumors in rats. In the present research, we investigated its mechanism of cytotoxicity to cancer cells.
Materials And Methods:
Molt-4 cells, in complete RPMI-1640 medium, were first incubated with 12 microM of human holotransferrin at 37 degrees C in a humid atmosphere of 5% CO2 for one hour. This enhanced the iron supply to the cells. The cells were then pelleted and transferred to a complete RPMI-1640 containing 200 microM of an analog dihydroartemisinin (DHA) and incubation was started (0 h). In addition, some culture samples were treated with holotransferrin alone and some (controls) were assayed without neither holotransferrin nor DHA treatment. Cells were counted and DNA diffusion assay was used to evaluate apoptosis and necrosis in each sample at 0 h and at 1, 2, 4 and 8 h of incubation.
Results:
DHA treatment significantly decreased cell counts and increased the proportion of apoptosis in cancer cells compared to controls (chi2=4.5, df=1, p<0.035). Addition of holotransferrin significantly further decreased cell counts (chi2=4.5, df=1, p<0.035) and increased apoptosis (chi2=4.5, df=1, p<0.035). No necrotic cells were observed.
Conclusion:
This rapid induction of apoptosis in cancer cells after treatment with DHA indicates that artemisinin and its analogs may be inexpensive and effective cancer agents.
Insights
Dihydroartemisinin (DHA), derived from artemisinin, rapidly induces apoptosis in cancer cells. Pre-treatment with holotransferrin enhances DHA
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Artemisinin, derived from Artemisia annua L., exhibits selective cancer cell cytotoxicity.
- Previous studies show artemisinin retards fibrosarcoma tumor growth in rats.
- This research investigates artemisinin's mechanism of cancer cell cytotoxicity.
Purpose of the Study:
- To investigate the mechanism of cytotoxicity of dihydroartemisinin (DHA) in cancer cells.
- To evaluate the effect of holotransferrin on DHA-induced cancer cell death.
- To determine if DHA induces apoptosis or necrosis.
Main Methods:
- Molt-4 cells were incubated with holotransferrin to enhance iron supply.
- Cells were subsequently treated with dihydroartemisinin (DHA).
- DNA diffusion assays assessed apoptosis and necrosis at various time points.
Main Results:
- DHA treatment significantly decreased cancer cell counts and increased apoptosis.
- Holotransferrin pre-treatment further reduced cell counts and enhanced apoptosis.
- No necrotic cells were observed in any treatment group.
Conclusions:
- Dihydroartemisinin (DHA) rapidly induces apoptosis in cancer cells.
- Artemisinin and its analogs show potential as inexpensive and effective cancer agents.
- The findings support further investigation of artemisinin derivatives for cancer therapy.
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