Biological Sciences Department, College of Science, King Faisal University, Al Ahsa 31982, Saudi Arabia.
Lab of Molecular Physiology, Zoology Department, Faculty of Science, Assiut University, Assiut 71515, Egypt.
Int J Mol Sci. 2022 Aug 30;23(17):9849. doi: 10.3390/ijms23179849.
Atropine (ATR) is extracted from a belladonna plant that belongs to a class of anticholinergic drugs and is therefore involved in the treatment of the overdose of cholinergic drugs or mushroom poisoning. It is a well-known blocker of muscarinic acetylcholine receptors (mAChRs) that are expressed in various tumor cells, including breast tumors from animal and human origin, but it has yet to be recommended as an anticancer drug. Our in silico docking analysis indicates that atropine has a roust virtual binding, with a stable binding energy, to two major signaling molecules involved in EMT regulation: E-cad and ZEB-2. For both, the gene and the protein expression level results show that atropine is an effective molecule in reducing epithelial-mesenchymal transition (EMT) and colony formation induced by TGF-B or carboplatin in both the mesenchymal-like cell line MDA-MB-231 and the epithelial-like cell line T47D. We conclude that atropine as a potential suppressor of EMT could be co-administrated with other chemotherapeutic drugs to reduce stemness in drug-resistant breast tumor cells.
阿托品（ATR）是从颠茄植物中提取的，颠茄植物属于抗胆碱能药物类，因此参与治疗过量的胆碱能药物或毒蕈中毒。它是一种众所周知的毒蕈碱乙酰胆碱受体（mAChR）阻断剂，在各种肿瘤细胞中表达，包括来自动物和人类的乳腺癌，但尚未被推荐为抗癌药物。我们的计算机对接分析表明，阿托品与 EMT 调节中涉及的两个主要信号分子 E-cad 和 ZEB-2 具有牢固的虚拟结合，具有稳定的结合能。对于这两种分子，基因和蛋白质表达水平的结果表明，阿托品可有效减少 TGF-β 或卡铂诱导的 EMT 和集落形成，在间充质样 MDA-MB-231 细胞系和上皮样 T47D 细胞系中均如此。我们得出结论，阿托品作为 EMT 的潜在抑制剂，可以与其他化疗药物联合使用，以降低耐药性乳腺癌细胞中的干性。
