Artemisinin and its derivatives, including
artesunate (ART) and
artemether (ARM), exert anticancer effects in the micromolar range in drug and radiation-resistant cell lines.
Artemisinin has been reported to sensitize
cervical cancer cells to
radiotherapy. In the present study, we determined whether ART and ARM could enhance the cytotoxicity of 5-aminolevulinic
acid (5-ALA)-based
photodynamic therapy (
PDT) against the mammary
tumor cells of mice. The corrected
PpIX fluorescence intensities in the control, 5-ALA, 5-ALA + ART, and 5-ALA + ARM groups were 3.385 ± 3.730, 165.7 ± 33.45, 139.0 ± 52.77, and 165.4 ± 51.10 a.u., respectively. At light doses of 3 and 5 J/cm2, the viability of 5-ALA-PDT-treated cells significantly decreased with ART (p < 0.01 and p < 0.01) and ARM treatment (p < 0.01 and p < 0.01). Besides, the number of
annexin V-FITC and
ethidium homodimer III-positive cells was greater in the 5-ALA-PDT with ARM group than that in the other groups.
N-acetylcysteine could not significantly inhibit the percentages of apoptotic cells or inviable cells induced by 5-ALA-PDT with ARM. These
reactive oxygen species-independent mechanisms might enhance cytotoxicity in 5-ALA-PDT with ARM-treated
tumor cells, suggesting that the use of 5-ALA-PDT with ARM could be a new strategy to enhance
PDT cytotoxicity against
tumor cells. However, as these results are only based on in vitro studies, further in vivo investigations are required.