Sari Anissa Nofita, Dhanjal Jaspreet Kaur, Elwakeel Ahmed, Kumar Vipul, Meidinna Hazna Noor, Zhang Huayue, Ishida Yoshiyuki, Terao Keiji, Sundar Durai, Kaul Sunil C, Wadhwa Renu
AIST-INDIA DAILAB, National Institute of Advanced Industrial Science & Technology (AIST), Central 5-41, Tsukuba 305-8565, Japan.
School of Integrative & Global Majors (SIGMA), Tsukuba Life Science Innovation, University of Tsukuba, Tsukuba 305-8577, Japan.
Cancers (Basel). 2022 Feb 3;14(3):787. doi: 10.3390/cancers14030787.
Withaferin A (Wi-A) and Caffeic Acid Phenethyl Ester (CAPE) are the bioactive ingredients of Ashwagandha () and propolis, respectively. Both of these natural compounds have been shown to possess anticancer activity. In the present study, we recruited a low dose of each of these compounds and developed a combination that exhibited remarkably potent anti-migratory and anti-angiogenic activities. Extensive molecular analyses including a cDNA array and expression analyses of the specific gene targets demonstrated that such activities are mediated through their effect on cell adhesion/tight junction proteins (Claudins, E-cadherin), inhibition of canonical Wnt/β-catenin signaling pathways and the consequent downregulation of EMT-signaling proteins (Vimentin, MMPs, VEGF and VEGFR) that play a critical role in cancer metastasis. The data supported that this novel combination of Wi-A and CAPE (Wi-ACAPE, containing 0.5 µM of Wi-A and 10 µM of CAPE) may be recruited for the treatment of metastatic and aggressive cancers and, hence, warrant further evaluation by recruiting a variety of experimental and clinical metastatic models.
冬凌草甲素（Wi-A）和咖啡酸苯乙酯（CAPE）分别是印度人参和蜂胶的生物活性成分。这两种天然化合物均已显示出具有抗癌活性。在本研究中，我们选用了低剂量的这两种化合物，并开发出一种组合，该组合表现出显著强效的抗迁移和抗血管生成活性。包括cDNA阵列和特定基因靶点表达分析在内的广泛分子分析表明，此类活性是通过它们对细胞黏附/紧密连接蛋白（闭合蛋白、E-钙黏蛋白）的作用、对经典Wnt/β-连环蛋白信号通路的抑制以及随后对在癌症转移中起关键作用的上皮-间质转化（EMT）信号蛋白（波形蛋白、基质金属蛋白酶、血管内皮生长因子和血管内皮生长因子受体）的下调来介导的。数据支持，这种新型的冬凌草甲素与咖啡酸苯乙酯组合（Wi-ACAPE，含有0.5μM的冬凌草甲素和10μM的咖啡酸苯乙酯）可用于治疗转移性和侵袭性癌症，因此，有必要通过纳入各种实验性和临床转移性模型进行进一步评估。
