Antimalarial Drugs Enhance the Cytotoxicity of 5-Aminolevulinic Acid-Based Photodynamic Therapy against the Mammary Tumor Cells of Mice In Vitro

• Main Authors: Tomohiro Osaki, Kiwamu Takahashi, Masahiro Ishizuka, Tohru Tanaka, Yoshiharu Okamoto
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Molecules
• Subjects: 5-aminolevulinic acid; artemisinin; artesunate; antimalarial; artemether; cytotoxicity; photodynamic therapy; reactive oxygen species
• Online Access: https://www.mdpi.com/1420-3049/24/21/3891

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 &#177; 3.730, 165.7 &#177; 33.45, 139.0 &#177; 52.77, and 165.4 &#177; 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 (<i>p</i> &lt; 0.01 and <i>p</i> &lt; 0.01) and ARM treatment (<i>p</i> &lt; 0.01 and <i>p</i> &lt; 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. <i>N</i>-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.