The mechanism of acetyl-L-carnitine on colorectal cancer and its metabolomic study

IF 3.4 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2026-05-15 Epub Date: 2026-01-21 DOI:10.1016/j.jpba.2026.117363

Jiayu Ning , Cuixin Cai , Xingxing Fan, Cuihua Liao, Mei Shen

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引用次数: 0

Abstract

Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Acetyl-L-carnitine (ALC), a natural form of L-carnitine, possesses anti-inflammatory, free radical-scavenging, and mitochondrial membrane-stabilizing properties. However, its precise mechanism of action in CRC remains unclear. To articulate the mechanism of action of ALC in CRC, we investigated its biological activity in HCT116 cells and a nude mouse xenograft model. The effects of ALC on HCT116 cells using CCK-8, colony formation, migration, invasion, and cell cycle assays. And detected oxidative stress-related indexes including reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). The inhibitory effect of ALC on colorectal tumor growth was further validated in a nude mouse xenograft model, and untargeted metabolomic analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The results showed that ALC can inhibit the proliferation and migration of HCT116 cells, induce cell cycle arrest and apoptosis, and affect the changes of oxidative stress indexes, and exacerbating cellular oxidative stress damage. In vivo experiments demonstrated that ALC effectively suppressed colorectal tumor growth in a dose-dependent manner. Plasma metabolomic analysis identified 10 differential metabolites between the ALC group and the control group, including meisoindigo, indole-3-acetaldehyde, etc., and 4 tumor differential metabolites, including L-proline, 3,4,5-Trimethoxytoluene, etc. Pathway enrichment analysis revealed that ALC altered 6 metabolic pathways in plasma, including tryptophan metabolism and glycine, serine, and threonine metabolism, and 5 pathways in tumor tissue, including arginine and proline metabolism and the sphingolipid signaling pathway. These findings provide novel theoretical evidence for the antitumor mechanisms of ALC in CRC.

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乙酰左旋肉碱对结直肠癌的作用机制及其代谢组学研究

结直肠癌（CRC）是世界范围内普遍存在的恶性肿瘤，其发病率和死亡率不断上升。乙酰左旋肉碱（ALC）是左旋肉碱的一种天然形式，具有抗炎、清除自由基和稳定线粒体膜的特性。然而，其在CRC中的确切作用机制尚不清楚。为了阐明ALC在结直肠癌中的作用机制，我们研究了其在HCT116细胞和裸鼠异种移植模型中的生物活性。利用CCK-8、集落形成、迁移、侵袭和细胞周期试验研究ALC对HCT116细胞的影响。检测氧化应激相关指标，包括活性氧（ROS）、谷胱甘肽（GSH）、丙二醛（MDA）、超氧化物歧化酶（SOD）。在裸鼠异种移植瘤模型中进一步验证ALC对结直肠癌肿瘤生长的抑制作用，并采用超高效液相色谱-串联质谱法进行非靶向代谢组学分析。结果表明，ALC可抑制HCT116细胞的增殖和迁移，诱导细胞周期阻滞和凋亡，影响氧化应激指标的变化，加重细胞氧化应激损伤。体内实验表明，ALC以剂量依赖的方式有效抑制结直肠肿瘤的生长。血浆代谢组学分析发现ALC组与对照组的差异代谢物有10种，包括异靛蓝、吲哚-3-乙醛等，肿瘤差异代谢物有4种，包括l -脯氨酸、3,4,5-三甲氧基甲苯等。途径富集分析显示，ALC改变了血浆中色氨酸代谢和甘氨酸、丝氨酸、苏氨酸代谢等6条代谢途径，改变了肿瘤组织中精氨酸、脯氨酸代谢和鞘脂信号通路等5条代谢途径。这些发现为ALC在结直肠癌中的抗肿瘤机制提供了新的理论依据。

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.