Fahmy Usama A, Fahmy Omar
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Urology Department, Universiti Putra Malaysia (UPM), Selangor, Malaysia.
Photodiagnosis Photodyn Ther. 2020 Jun;30:101714. doi: 10.1016/j.pdpdt.2020.101714. Epub 2020 Mar 9.
5-Aminolevulinic (5-ALA) may be used as a photo diagnostic agent in bladder cancer. The aim of this study was to investigate the cytotoxic effect of 5-ALA on bladder cancer cells.
T24 cells treated with various concentrations of mitomycin (MC), 5-ALA and an MC/5-ALA mixture were evaluated to determine the role of 5-ALA on MC cytotoxicity. Cell cycle analysis was conducted, and apoptosis was analyzed by flow cytometry. Caspase 3 enzyme and reactive oxygen species were measured.
Our initial studies exploring the impact of combination therapy on cell viability demonstrated improved cytotoxic effects on T24 and RT cells with relatively low doses of 5-ALA/MC in conjunction with MC alone. Indicated no significant difference between the IC50 of MC and MC/5-ALA in T24 cells, while IC50 value was decreased by 25 % in RT4 cells in 5-ALA/MC in comparing with MC alone. However, examination of cell cycle phase arrests by flow cytometry revealed significant PreG1 apoptosis and cell growth arrest in G2/M in T24 cells treated with the MC/5-ALA mixture compared with MC treatment. In addition, caspase 3 enzyme was increased by 1.15-fold in T24 cells treated with MC/5-ALA in comparison with MC alone.
These results suggest that 5-ALA might possess anti-cancer properties and is not only a photo diagnostic element.
5-氨基乙酰丙酸(5-ALA)可作为膀胱癌的光诊断剂。本研究的目的是探讨5-ALA对膀胱癌细胞的细胞毒性作用。
对用不同浓度的丝裂霉素(MC)、5-ALA以及MC/5-ALA混合物处理的T24细胞进行评估,以确定5-ALA对MC细胞毒性的作用。进行细胞周期分析,并通过流式细胞术分析细胞凋亡。检测半胱天冬酶3酶和活性氧。
我们初步研究联合治疗对细胞活力的影响,结果表明,与单独使用MC相比,相对低剂量的5-ALA/MC联合使用时,对T24和RT细胞具有更好的细胞毒性作用。T24细胞中MC和MC/5-ALA的半数抑制浓度(IC50)无显著差异,而与单独使用MC相比,5-ALA/MC处理的RT4细胞的IC50值降低了25%。然而,通过流式细胞术检测细胞周期阻滞发现,与MC处理相比,用MC/5-ALA混合物处理的T24细胞中出现显著的G1期前凋亡和G2/M期细胞生长停滞。此外,与单独使用MC相比,用MC/5-ALA处理的T24细胞中的半胱天冬酶3酶增加了1.15倍。
这些结果表明,5-ALA可能具有抗癌特性,且不仅是一种光诊断元素。