Herrera-Calderon Oscar, Yepes-Pérez Andres F, Quintero-Saumeth Jorge, Rojas-Armas Juan Pedro, Palomino-Pacheco Miriam, Ortiz-Sánchez José Manuel, Cieza-Macedo Edwin César, Arroyo-Acevedo Jorge Luis, Figueroa-Salvador Linder, Peña-Rojas Gilmar, Andía-Ayme Vidalina
Academic Department of Pharmacology, Bromatology and Toxicology, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Jr Puno 1002, Lima 15001, Peru.
Chemistry of Colombian Plants, Institute of Chemistry, Faculty of Exact and Natural Sciences, University of Antioquia-UdeA, Calle 70 No. 52-21 A.A, Medellin 1226, Colombia.
Evid Based Complement Alternat Med. 2020 Oct 26;2020:8830665. doi: 10.1155/2020/8830665. eCollection 2020.
Carvacrol is a phenol monoterpene found in aromatic plants specially in Lamiaceae family, which has been evaluated in an experimental model of breast cancer. However, any proposed mechanism based on its antitumor effect has not been reported. In our previous study, carvacrol showed a protective effect on 7,12-dimethylbenz[]anthracene- (DMBA-) induced breast cancer in female rats. The main objective in this research was to evaluate by using study the carvacrol on HER2, PI3K, mTOR, hER-, PR, and EGFR receptors involved in breast cancer progression by docking analysis, molecular dynamic, and drug-likeness evaluation. A multilevel computational study to evaluate the antitumor potential of carvacrol focusing on the main targets involved in the breast cancer was carried out. The study starts with protein-ligand docking of carvacrol followed by ligand pathway calculations, molecular dynamic simulations, and molecular mechanics energies combined with the Poisson-Boltzmann (MM/PBSA) calculation of the free energy of binding for carvacrol. As result, the study led to the identification of carvacrol with strong binding affinity on mTOR receptor. Additionally, drug-likeness index for carvacrol showed a good predicted therapeutic profile of druggability. Our findings suggest that mTOR signaling pathway could be responsible for its preventive effect in the breast cancer.
香芹酚是一种酚类单萜，存在于芳香植物中，尤其是唇形科植物中，它已在乳腺癌实验模型中得到评估。然而，尚未有基于其抗肿瘤作用提出的任何机制的报道。在我们之前的研究中，香芹酚对7,12-二甲基苯并[a]蒽（DMBA）诱导的雌性大鼠乳腺癌显示出保护作用。本研究的主要目的是通过对接分析、分子动力学和药物相似性评估，研究香芹酚对参与乳腺癌进展的HER2、PI3K、mTOR、hER-、PR和EGFR受体的影响。开展了一项多层次计算研究，以评估香芹酚针对乳腺癌主要靶点的抗肿瘤潜力。该研究首先进行香芹酚的蛋白质-配体对接，随后进行配体途径计算、分子动力学模拟以及结合泊松-玻尔兹曼（MM/PBSA）计算香芹酚结合自由能的分子力学能量计算。结果，该研究确定香芹酚对mTOR受体具有强结合亲和力。此外，香芹酚的药物相似性指数显示出良好的可成药预测治疗概况。我们的研究结果表明，mTOR信号通路可能是其对乳腺癌预防作用的原因。
