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龙须菜化合物靶向肺腺癌中的NFκB级联反应。

Gelidiella acerosa Compounds Target NFκB Cascade in Lung Adenocarcinoma.

作者信息

Begum S M Fazeela Mahaboob, Hemalatha S

机构信息

School of Life Sciences, B.S. Abdur Rahman Crescent Institute of Science and Technology, Chennai, 600048, India.

Department of Biochemistry, New Prince Shri Bhavani Arts and Science College, Chennai, India.

出版信息

Appl Biochem Biotechnol. 2022 Apr;194(4):1566-1579. doi: 10.1007/s12010-021-03761-z. Epub 2021 Nov 22.

DOI:10.1007/s12010-021-03761-z
PMID:34811638
Abstract

In carcinogenesis, increased metabolism, abnormal functioning of mitochondria, peroxisomes, aberrant cell signaling, and prolonged inflammation can result in the overproduction of reactive oxygen species (ROS). In turn, excess ROS can upregulate the expression of various signaling pathways including the MAP kinase, PI3K/Akt, and NFκB cascades in cancer. The constitutive expression of NFκB causes drug resistance in lung cancer. Hence, drugs that can enhance the antioxidant activity of enzymes and regulate the NFκB activity are of prime target to manage the drug resistance and inflammation in cancer. This study evaluated the effect of compounds present in ethyl acetate extract of Gelidiella acerosa on inflammation and on antioxidant enzymes in lung cancer. The anti-inflammatory activity was determined under in silico and in vitro conditions. The in silico analysis showed that the phyto-constituents of G. acerosa inhibit the IKBα-NFκB-p65-p50 complex in a similar way as that of doxorubicin and dexamethasone. Similarly, G. acerosa treatment enhanced the efficiency of antioxidant enzymes peroxidases and superoxide dismutase in A549 lung cancer cells. Furthermore, the results of in vitro analysis showed that G. acerosa can decrease the activation of NFκB and production of pro-inflammatory cytokines and upregulate the expression of IL 10. As inflammation causes cancer progression, the inhibition of inflammation inhibits tumorigenesis. Hence, based on the results of the study, it can be concluded that G. acerosa exerts anti-inflammatory activity by decreasing the expression of NFκB cascade and moreover, the phyto-constituents of G. acerosa may have the potential to regulate the inflammatory response.

摘要

在致癌过程中,新陈代谢加快、线粒体和过氧化物酶体功能异常、细胞信号传导异常以及炎症持续时间延长可导致活性氧(ROS)过度产生。反过来,过量的ROS可上调癌症中各种信号通路的表达,包括丝裂原活化蛋白激酶(MAP激酶)、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)和核因子κB(NFκB)级联反应。NFκB的组成性表达导致肺癌产生耐药性。因此,能够增强酶的抗氧化活性并调节NFκB活性的药物是管理癌症耐药性和炎症的主要靶点。本研究评估了鹿角菜乙酸乙酯提取物中所含化合物对肺癌炎症和抗氧化酶的影响。在计算机模拟和体外条件下测定抗炎活性。计算机模拟分析表明,鹿角菜的植物成分以与阿霉素和地塞米松类似的方式抑制IκBα-NFκB-p65-p50复合物。同样,鹿角菜处理提高了A549肺癌细胞中抗氧化酶过氧化物酶和超氧化物歧化酶的效率。此外,体外分析结果表明,鹿角菜可降低NFκB的激活和促炎细胞因子的产生,并上调白细胞介素10的表达。由于炎症会导致癌症进展,抑制炎症可抑制肿瘤发生。因此,根据该研究结果可以得出结论,鹿角菜通过降低NFκB级联反应的表达发挥抗炎活性,此外,鹿角菜的植物成分可能具有调节炎症反应的潜力。

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