Antimalarial Drugs Enhance the Cytotoxicity of 5-Aminolevulinic Acid-Based Photodynamic Therapy against the Mammary Tumor Cells of Mice In Vitro
Antimalarial Drugs Enhance the Cytotoxicity of 5-Aminolevulinic Acid-Based Photodynamic Therapy against the Mammary Tumor Cells of Mice In Vitro
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DOI：
10.3390/molecules24213891
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发表时间：
2019-11-01
期刊：
影响因子：
4.6
通讯作者：
Okamoto, Yoshiharu
中科院分区：
文献类型：
--
作者：
Osaki, Tomohiro;Takahashi, Kiwamu;Okamoto, Yoshiharu
青蒿素及其衍生物，包括青蒿琥酯（ART）和蒿甲醚（ARM），在耐药和耐辐射细胞系中发挥微摩尔范围内的抗癌作用。据报道，青蒿素使宫颈癌细胞对放射治疗敏感。在本研究中，我们研究了ART和ARM是否可以增强5-氨基乙酰丙酸（5-ALA）光动力疗法（PDT）对小鼠乳腺肿瘤细胞的细胞毒性。对照组、5-ALA组、5-ALA + ART组和5-ALA + ARM组的校正PpIX荧光强度分别为3.385 +/- 3.730、165.7 +/- 33.45、139.0 +/- 52.77和165.4 +/- 51.10 a.u.。在3和5 J/cm(2)轻剂量下，ART （p < 0.01和p < 0.01）和ARM （p < 0.01和p < 0.01）处理5- ala - pdt的细胞活力显著降低。5-ALA-PDT联合ARM组膜联蛋白V-FITC和乙啶同型二聚体iii阳性细胞数量明显高于其他各组。n -乙酰半胱氨酸不能显著抑制5-ALA-PDT联合ARM诱导的凋亡细胞和不存活细胞的百分比。这些与活性氧无关的机制可能会增强5-ALA-PDT与ARM处理的肿瘤细胞的细胞毒性，这表明5-ALA-PDT与ARM联合使用可能是增强PDT对肿瘤细胞毒性的一种新策略。然而，由于这些结果仅基于体外研究，因此需要进一步的体内研究。
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/cm(2), 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.