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通过计算机模拟和体外研究相结合揭示辣椒素对人碳酸酐酶同工酶IX和XII的新型抑制活性

Uncovering Novel Capsaicin Inhibitory Activity towards Human Carbonic Anhydrase Isoforms IX and XII by Combining In Silico and In Vitro Studies.

作者信息

Gualtieri Gianmarco, Maruca Annalisa, Rocca Roberta, Carta Fabrizio, Berrino Emanuela, Salatino Alessandro, Brescia Carolina, Torcasio Roberta, Crispo Manuel, Trapasso Francesco, Alcaro Stefano, Supuran Claudiu T, Costa Giosuè

机构信息

Dipartimento di Scienze della Salute, Università "Magna Græcia" di Catanzaro, Viale Europa, 88100 Catanzaro, Italy.

Associazione CRISEA-Centro di Ricerca e Servizi Avanzati per l'Innovazione Rurale, Località Condoleo di Belcastro, 88055 Catanzaro, Italy.

出版信息

Antioxidants (Basel). 2023 May 18;12(5):1115. doi: 10.3390/antiox12051115.

DOI:10.3390/antiox12051115
PMID:37237982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10215620/
Abstract

Hot pepper () represents one of the most widespread functional foods of the Mediterranean diet, and is associated with a reduced risk of developing cardiovascular disease, cancer, and mental disorders. In particular, its bioactive spicy molecules, named Capsaicinoids, exhibit polypharmacological properties. Among them, Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the most studied and reported in variegated scientific contributions for its beneficial effects, often linked to mechanisms of action unrelated to the activation of Transient Receptor Potential Vanilloid 1 (TRPV1). In this study, we present the application of in silico methods to Capsaicin for evaluating its inhibitory activity against the tumor-associated human () expressed CA IX and XII. In vitro assays confirmed Capsaicin inhibitory activity towards the most relevant tumor-related CA isoforms. In particular, the CAs IX and XII showed an experimental K value of 0.28 μM and 0.064 μM, respectively. Then, an A549 model of non-small cell lung cancer, typically characterized by an elevated expression of CA IX and XII, was employed to test the inhibitory effects of Capsaicin in vitro under both normoxic and hypoxic conditions. Finally, the migration assay revealed that Capsaicin [10 µM] inhibits cells from moving in the A549 cells model.

摘要

辣椒是地中海饮食中最普遍的功能性食品之一，与降低患心血管疾病、癌症和精神障碍的风险有关。特别是，其具有生物活性的辛辣分子辣椒素类化合物具有多种药理特性。其中，辣椒素（反式-8-甲基-N-香草基-6-壬酰胺）是研究最多的，并且在各种科学文献中因其有益作用而被报道，这些作用通常与瞬时受体电位香草酸亚型1（TRPV1）的激活无关的作用机制有关。在本研究中，我们展示了利用计算机模拟方法对辣椒素进行研究，以评估其对肿瘤相关的人碳酸酐酶（CA）IX和XII的抑制活性。体外试验证实了辣椒素对最相关的肿瘤相关CA亚型的抑制活性。特别是，CA IX和XII的实验K值分别为0.28 μM和0.064 μM。然后，采用通常以CA IX和XII高表达为特征的非小细胞肺癌A549模型，在常氧和低氧条件下体外测试辣椒素的抑制作用。最后，迁移试验表明，10 μM的辣椒素可抑制A549细胞模型中的细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/00607ca0e1d4/antioxidants-12-01115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/37572db9d027/antioxidants-12-01115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/d5a9fba3b835/antioxidants-12-01115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/f6948ac45fbc/antioxidants-12-01115-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/00607ca0e1d4/antioxidants-12-01115-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/37572db9d027/antioxidants-12-01115-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/d5a9fba3b835/antioxidants-12-01115-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/f6948ac45fbc/antioxidants-12-01115-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7f/10215620/bbec4abcea35/antioxidants-12-01115-g004.jpg
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