Chen Shan-Mei, Feng Jun-Nan, Zhao Chuan-Ke, Yao Li-Cheng, Wang Li-Xin, Meng Lin, Cai Shao-Qing, Liu Cai-Yun, Qu Li-Ke, Jia Yan-Xing, Shou Cheng-Chao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute Beijing, China.
Key Laboratory of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou, China.
Am J Cancer Res. 2022 Nov 15;12(11):4930-4953. eCollection 2022.
Cancer is one of the main causes of death in humans worldwide, the development of more effective anticancer drugs that can inhibit the malignant progression of cancer cells is of great significance. Aiphanol is a natural product identified from the seeds of and the rhizome of . Our preliminary studies revealed that it had potential antiangiogenic and antilymphangiogenic activity by directly targeting VEGFR2/3 and COX2 in endothelial cells. However, the influence of aiphanol on cancer cells per se remains largely undefined. In this study, the effects and related mechanisms of aiphanol on cancer growth and metastasis were evaluated and . Acute toxicity assay and pharmacokinetic analysis were utilized to investigate the safety profile and metabolism characteristics of aiphanol. We revealed that aiphanol inhibited the proliferation of various types of cancer cells and the growth of xenograft tumors in mice and zebrafish models. The possible mechanism was associated with the inactivation of multiple kinases, including FAK, AKT and ERK, and the upregulation of BAX and cleaved caspase-3 to promote cancer cell apoptosis. Aiphanol significantly inhibited cancer cell migration and invasion, which was related to the inhibition of epithelial-mesenchymal transition (EMT) and F-actin aggregation. Aiphanol effectively attenuated the metastasis of several types of cancer cells . In addition, aiphanol exerted no significant toxicity and had fast metabolism. Collectively, we demonstrated the anticancer effects of aiphanol and suggested that aiphanol has potential as a safe and effective therapeutic agent to treat cancer.
癌症是全球人类主要死因之一，研发出更有效的能抑制癌细胞恶性进展的抗癌药物具有重要意义。爱番诺是从[植物名称1]种子和[植物名称2]根茎中鉴定出的一种天然产物。我们的初步研究表明，它通过直接作用于内皮细胞中的血管内皮生长因子受体2/3（VEGFR2/3）和环氧化酶2（COX2），具有潜在的抗血管生成和抗淋巴管生成活性。然而，爱番诺对癌细胞本身的影响在很大程度上仍不明确。在本研究中，评估了爱番诺对癌症生长和转移的影响及相关机制[此处可能有遗漏信息未完整给出]。采用急性毒性试验和药代动力学分析来研究爱番诺的安全性和代谢特征。我们发现爱番诺在小鼠和斑马鱼模型中可抑制多种类型癌细胞的增殖以及异种移植肿瘤的生长。可能的机制与多种激酶的失活有关，包括黏着斑激酶（FAK）、蛋白激酶B（AKT）和细胞外信号调节激酶（ERK），以及促凋亡蛋白BAX和裂解的半胱天冬酶-3的上调以促进癌细胞凋亡。爱番诺显著抑制癌细胞的迁移和侵袭，这与抑制上皮-间质转化（EMT）和F-肌动蛋白聚集有关。爱番诺有效减弱了几种类型癌细胞的转移[此处可能有遗漏信息未完整给出]。此外，爱番诺没有显著毒性且代谢迅速。总体而言，我们证明了爱番诺的抗癌作用，并表明爱番诺有潜力成为一种安全有效的抗癌治疗药物。
