玫瑰酚通过抑制 P13K/AKT/HMBG1 信号通路触发细胞凋亡,防止 MNNG 诱导的大鼠胃癌发生

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Yan-Bang Niu, Periyannan Velu, Awais Khalid, Samer H Zyoud, Mohsin Kazi, Yuzhu Li
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引用次数: 0

摘要

背景胃癌(GC)是中国常见的恶性肿瘤。尽管有许多治疗方法可以改善胃癌患者的健康状况,但其疗效仍显不足:玫瑰酚(RML)是一种酚类二萜化合物,具有抗氧化和抗癌活性。本研究测定了 RML 对甲基硝基亚硝基胍(MNNG)诱导的 GC 模型的凋亡功效:将大鼠分为四组,即正常对照组、MNNG(200 毫克/千克体重)+氯化钠组、MNNG + RML(20 毫克/千克)组和口服 RML(20 毫克/千克)治疗 20 周组:结果表明,GC 大鼠的 PC 含量较高:此外,RML 通过使 PI3K/AKT/HMGB1 通路失活,引发由 Caspase 介导的线粒体凋亡,最终导致 GC 细胞死亡。这表明 RML 可能是一种潜在的天然抗氧化剂,可用作 GC 大鼠的化学保护剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Rosmanol Triggers Apoptosis Against MNNG-induced Gastric Carcinogenesis in Rats through Attenuation of the P13K/AKT/HMBG1 Signaling Pathway.

Background: Gastric cancer (GC) is a frequent malignant neoplasm found in China. Despite numerous therapeutic methodologies to ameliorate the well-being of GC patients, their efficiency remains inadequate.

Objective: Rosmanol (RML) is a phenolic diterpene compound with antioxidant and anticancer activities. In the current research, the apoptotic efficacy of RML on methylnitronitrosoguanidine (MNNG)-induced GC model was determined.

Materials and methods: The rats were allocated into four sets, viz., normal control, MNNG (200 mg/kg bw) + NaCl, MNNG + RML (20 mg/kg), and RML (20 mg/kg) orally treated for 20 weeks.

Results: The results exposed that GC rats revealed higher (P<0.05) levels of TBARS and reduced antioxidant status in the stomach and liver tissues counter to other groups. In contrast, the TBARS level was substantially alleviated (P<0.05) and restored the antioxidant status in RMLadministered rats. Histopathologic assessment of gastric tissue unveiled that an MNNG-induced group presented squamous cell carcinoma with keratin pearls. The administration of RML reduced GC incidence, and only mild dysplasia was observed. Further, RML alleviated Bcl-2, P13K, AKT, and HMGB1, as evidenced by RT-PCR and Western blot analysis.

Conclusion: Furthermore, RML triggered caspase-mediated mitochondrial apoptosis through the inactivation of the PI3K/AKT/HMGB1 pathway, eventually leading to GC cell death. This highlights that RML may be a potential natural antioxidant employed as a chemoprotective agent in GC rats.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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