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来自紫铆树的免疫调节凝集素靶向PI3K/AKT信号介导的凋亡,以在体内和体外使肿瘤消退。

Immunomodulatory lectin from Cordia myxa targets PI3K/AKT signalling mediated apoptosis to regress both in-vitro and in-vivo tumour.

作者信息

Siddesh B M, Kiran B K, Sherapura Ankith, Mahmood Riaz, Suchetha Kumari N, Prabhakar B T

机构信息

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, Karnataka, India.

Postgraduate Department of Studies and Research in Biotechnology and Bioinformatics, Kuvempu University, Shankaraghatta, Karnataka, India.

出版信息

Int J Biol Macromol. 2025 Mar;294:139433. doi: 10.1016/j.ijbiomac.2024.139433. Epub 2025 Jan 6.

Abstract

Plant based medicine is gaining recognition as a complementary approach to conventional treatments. Plants contain lectins that bind to carbohydrates and exhibit various biological properties and being used in cancer treatment. In present investigation Cordia myxa fruit was chosen, screen for presence of lectin and explore its biological role. Screening of lectin was conducted through HA activity. Purification and characterization through conventional methods. HI assay to confirm the carbohydrate specificity. Immunomodulatory role by proliferative assays and ELISA. Apoptosis by annexin-V stain, TUNEL, MOMP and COMET assay and in-vivo antitumour activity by EAC induced ascites and solid tumour model. Gene expression through IB and IHC. The results illustrated that, presence of immunostimulant, ̴12 kDa lectin (CML) with strong leucoaggulutination activity having ovalbumin & fetuin specificity. The CML exhibits immune cell proliferation and secretes immune cytokines IL-2, IL-10 & IL-12. The immunomodulatory experiments infer that, CML induces anti-proliferative response against A549 and EAC by inducing apoptosis, which were validated in an in-vitro & in-vivo models. Mechanistically, CML modulates phosphorylation of PI3K/AKT signalling pathways and modulates downstream apoptotic proteins P53, Bax, Bad, Bcl-2, cytochrome-c, caspase-3 and DFF-40. Overall, the study reports the immunomodulatory lectin in Cordia myxa with its potential therapeutic role.

摘要

植物性药物作为传统治疗的补充方法正逐渐获得认可。植物含有与碳水化合物结合并具有多种生物学特性的凝集素,目前正被用于癌症治疗。在本研究中,选择了刺果紫麻果实,筛选其中凝集素的存在并探索其生物学作用。通过血凝活性筛选凝集素。采用传统方法进行纯化和表征。通过血凝抑制试验确认碳水化合物特异性。通过增殖试验和酶联免疫吸附测定评估免疫调节作用。通过膜联蛋白-V染色、末端脱氧核苷酸转移酶介导的缺口末端标记法、线粒体膜电位检测和彗星试验检测细胞凋亡,并通过艾氏腹水癌诱导的腹水和实体瘤模型评估体内抗肿瘤活性。通过免疫印迹和免疫组化检测基因表达。结果表明,存在一种免疫刺激剂,即分子量约为12 kDa的凝集素(CML),具有较强的白细胞凝集活性,对卵清蛋白和胎球蛋白具有特异性。CML可促进免疫细胞增殖并分泌免疫细胞因子IL-2、IL-10和IL-12。免疫调节实验表明,CML通过诱导细胞凋亡对A549和艾氏腹水癌细胞产生抗增殖反应,这在体外和体内模型中均得到验证。从机制上讲,CML调节PI3K/AKT信号通路的磷酸化,并调节下游凋亡蛋白P53、Bax、Bad、Bcl-2、细胞色素c、半胱天冬酶-3和DNA片段化因子40。总体而言,该研究报道了刺果紫麻中的免疫调节凝集素及其潜在的治疗作用。

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