5-Amino-4-oxopentanoic acid is a naturally occurring non-proteinogenic amino acid and a prodrug of the photosensitizer protoporphyrin IX (PpIX). 5-Amino-4-oxopentanoic acid can be activated by laser light at a wavelength of about 635nm (580 to 740nm) to emit red fluorescence (620 to 710nm), and can be used as a photodiagnostic agent for a variety of cancers[1-4].
5-Amino-4-oxopentanoic acid can inhibit the viability of U87MG cells with an IC50 of 500μg/mL. 5-Amino-4-oxopentanoic acid (250μg/mL) can induce apoptosis of U87MG cells, promote the expression of Bax and p53, and inhibit the expression of Bcl-2. 5-Amino-4-oxopentanoic acid increased the accumulation of U87MG cells in the SUB-G1 population, reduced the expression of cyclin D1, and reduced the migration ability of U87MG cells[2]. When using photodynamic therapy, HCC cells were treated with different concentrations (0-0.6mM) of 5-Amino-4-oxopentanoic acid at different illumination doses (0-3.6J/cm2). 5-Amino-4-oxopentanoic acid inhibited the viability of HCC cells in a dose-dependent manner[3].
5-Amino-4-oxopentanoic acid (200mg/kg)-mediated photodynamic therapy can inhibit the growth rate of mouse tumors in the SCID mouse hepatocellular carcinoma model[3]. 5-Amino-4-oxopentanoic acid (30 or 300mg/kg/day) can promote caspase 3-dependent apoptosis in the carcinogenesis of transgenic prostate adenocarcinoma (FVB-TRAMP) mice by supporting the functional expression of mitochondrial cytochrome c and cytochrome c oxidase subunit 4 (COX4), thereby reducing the tumor burden in mice[4].
References:
[1] Pignatelli P, Umme S, D’Antonio D L, et al. Reactive oxygen species produced by 5-aminolevulinic acid photodynamic therapy in the treatment of cancer[J]. International Journal of Molecular Sciences, 2023, 24(10): 8964.
[2] Jalili-Nik M, Abbasinezhad-Moud F, Sahab-Negah S, et al. Antitumor effects of 5-Aminolevulinic acid on human malignant glioblastoma cells[J]. International Journal of Molecular Sciences, 2021, 22(11): 5596.
[3] Kumar A, Pecquenard F, Baydoun M, et al. An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma[J]. International Journal of Molecular Sciences, 2023, 24(13): 10426.
[4] Onishi K, Miyake M, Tatsumi Y, et al. Inhibitory Effect of Orally Administered 5-Aminolevulinic Acid on Prostate Carcinogenesis in the FVB-Transgenic Adenocarcinoma of a Mouse Prostate (FVB-TRAMP) Model[J]. Asian Pacific Journal of Cancer Prevention: APJCP, 2020, 21(12): 3743.
5-Amino-4-oxopentanoic acid是一种天然存在的非蛋白原性氨基酸，是光敏剂原卟啉IX（PpIX）的前药。5-Amino-4-oxopentanoic acid可以被波长约为635nm（580至740nm）的激光激活，发出红色荧光（620至710nm），作为多种癌症的光诊断剂[1-4]。
5-Amino-4-oxopentanoic acid可抑制U87MG细胞的活力，IC50为500μg/mL。5-Amino-4-oxopentanoic acid（250μg/mL）可诱导U87MG细胞凋亡，促进Bax和p53表达，抑制Bcl-2表达。5-Amino-4-oxopentanoic acid增加了U87MG 细胞在SUB-G1群体中的积累，降低了细胞周期蛋白D1的表达，降低了U87MG细胞的迁移能力[2]。使用光动力疗法时，在不同照明剂量（0-3.6J/cm2）下使用不同浓度（0-0.6mM）的5-Amino-4-oxopentanoic acid处理HCC细胞，5-Amino-4-oxopentanoic acid以剂量依赖性的方式抑制HCC细胞活力[3]。
5-Amino-4-oxopentanoic acid（200mg/kg）介导的光动力疗法可抑制SCID小鼠肝细胞癌模型中小鼠肿瘤的生长速率[3]。5-Amino-4-oxopentanoic acid（30或300mg/kg/day）可通过支持线粒体细胞色素c和细胞色素c氧化酶亚基4（COX4）的功能表达，促进转基因小鼠前列腺腺癌（FVB-TRAMP）小鼠癌变中caspase 3依赖性细胞凋亡，从而减轻小鼠肿瘤负荷[4]。