Graduate School of Advanced Technology and Science, Tokushima University, Tokushima, Japan.
Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Photodiagnosis Photodyn Ther. 2017 Dec;20:182-188. doi: 10.1016/j.pdpdt.2017.10.014. Epub 2017 Oct 19.
5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), is now widely used for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various cancers. Recently, we found that treatment of cancer cells with the Schiff base derivative TX-816 along with ALA could significantly increase the efficacy of ALA-PDT. This enhancing effect of TX-816 on ALA-PDT is attributed to 3,5-dichlorosalicylaldehyde (DCSA), a molecule produced by the degradation of TX-816. Similar to TX-816, DCSA significantly enhances the effect of ALA-PDT. Furthermore, DCSA could restore the sensitivity of cancer cells that acquired resistance to ALA-PDT. These results indicate that DCSA, as well as TX-816, is a potent lead compound for the development of an ALA-PDT sensitizer. TX-816 might be a useful compound for designing prodrug-type ALA-PDT enhancers.
5-氨基酮戊酸（ALA）是原卟啉 IX（PpIX）的前体，现已广泛用于各种癌症的光动力诊断（ALA-PDD）和光动力治疗（ALA-PDT）。最近，我们发现用席夫碱衍生物 TX-816 联合 ALA 处理癌细胞，可以显著提高 ALA-PDT 的疗效。TX-816 对 ALA-PDT 的这种增强作用归因于 3,5-二氯水杨醛（DCSA），这是 TX-816 降解产生的一种分子。与 TX-816 类似，DCSA 显著增强了 ALA-PDT 的效果。此外，DCSA 可以恢复对 ALA-PDT 产生耐药性的癌细胞的敏感性。这些结果表明，DCSA 与 TX-816 一样，是开发 ALA-PDT 敏化剂的有效先导化合物。TX-816 可能是设计前药型 ALA-PDT 增强剂的有用化合物。
