Fayyaz Sundas, Aydin Tuba, Cakir Ahmet, Gasparri Maria Luisa, Panici Pierluigi Benedetti, Farooqi Ammad Ahmad
Department of Gynecologic- Obstetrical and Urologic Sciences, "Sapienza" University of Rome, Rome, Italy.
Curr Top Med Chem. 2016;16(22):2477-83. doi: 10.2174/1568026616666160212123706.
Cancer is a multifaceted and genomically complex disease. Rapidly accumulating preclinical and clinical studies are emphasizing on wide ranging molecular mechanisms that underpin cancer development, progression and metastasis. Intratumor heterogeneity, loss of apoptosis, rapidly developing resistance against molecular therapeutics and off-target effects are some of the deeply studied resistance mechanisms. Data obtained through high-throughput technologies has considerably enhanced our understanding of the intracellular signaling cascades frequently dysregulated spatio-temporally. There is an ever-expanding list of synthetic and natural agents reported to activate tumor suppressor genes and inhibit oncogenes in cancer cells. Markedly reduced tumor growth has also been documented in xenografted mice administered with phytochemicals. Oleuropein is a bioactive ingredient isolated from various sources and there is evidence of complete regression of tumors in 9- 12 days in mice orally administered with Oleuropein. In this review we summarize recent developments in use of Oleuropein as an anticancer agent. Extraction and isolation of Oleuropein and how it modulates intracellular signaling network to induce apoptosis in cancer cells. Human epidermal growth factor receptor 2 (HER2) frequently overexpressed in breast cancer cells is inhibited by Oleuropein. Interestingly, trastuzumab efficacy was notably enhanced in Oleuropein treated breast cancer cells. There is still insufficient information related to Oleuropein mediated microRNA regulation in cancer cells. We still do not have information about regulation of different signaling cascades by Oleuropein which are deregulated in cancer. Future studies must converge on a deeper analysis of target molecular network of Oleuropein and its efficacy as a tumor growth inhibitor in xenografted mice.
癌症是一种多方面且基因组复杂的疾病。快速积累的临床前和临床研究强调了支撑癌症发生、发展和转移的广泛分子机制。肿瘤内异质性、凋亡缺失、对分子疗法迅速产生的耐药性以及脱靶效应是一些深入研究的耐药机制。通过高通量技术获得的数据极大地增进了我们对经常在时空上失调的细胞内信号级联反应的理解。据报道，激活肿瘤抑制基因并抑制癌细胞中癌基因的合成和天然药物的清单不断增加。在给予植物化学物质的异种移植小鼠中也记录到肿瘤生长明显减少。橄榄苦苷是从各种来源分离出的一种生物活性成分，有证据表明口服橄榄苦苷的小鼠在9至12天内肿瘤完全消退。在本综述中，我们总结了橄榄苦苷作为抗癌剂使用的最新进展。橄榄苦苷的提取和分离以及它如何调节细胞内信号网络以诱导癌细胞凋亡。在乳腺癌细胞中经常过度表达的人表皮生长因子受体2（HER2）受到橄榄苦苷的抑制。有趣的是，在经橄榄苦苷处理的乳腺癌细胞中，曲妥珠单抗的疗效显著增强。关于橄榄苦苷介导的癌细胞中微小RNA调节的信息仍然不足。我们仍然没有关于橄榄苦苷对癌症中失调的不同信号级联反应的调节信息。未来的研究必须集中于对橄榄苦苷的靶分子网络及其作为异种移植小鼠中肿瘤生长抑制剂的疗效进行更深入的分析。
