Novel natural product therapeutics targeting both inflammation and cancer.
Novel natural product therapeutics targeting both inflammation and cancer.
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DOI：
10.1016/s1875-5364(17)30062-6
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发表时间：
2017-06
影响因子：
4.6
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Qin J;Wang W;Zhang R
炎症最近被认为是人类癌症的标志之一。慢性炎症反应在癌症的发生、进展、转移和化疗耐药中发挥着关键作用。相反，致癌畸变也会产生炎症微环境，促进癌症的发生和进展。由于致癌基因和促炎基因之间复杂的串扰，导致炎症性癌症和癌症相关炎症的分子作用机制尚未完全了解。然而，调节炎症和癌症的分子介质，例如 NF-κB 和 STAT，已被认为是预防和治疗这些疾病的有希望的靶标。最近的工作进一步证明了癌基因（例如，NFAT1、MDM2）和抑癌基因（例如，p53）在癌症相关炎症中的重要作用。针对这些分子介质的天然产物在临床前和临床研究中已显示出抗癌和抗炎活性。倍半萜类化合物（STs）是一类新型植物次级代谢产物，因其化学结构和药理活性的多样性，近年来引起了人们的极大兴趣。目前，我们和其他研究人员发现，二聚倍半萜类化合物（DST）由于烷基化中心数量的增加以及构象灵活性和亲脂性的改善，可能会增强对分子靶标的活性和结合亲和力。在这里，我们重点讨论 ST 和 DST 在治疗炎症和癌症中的活性和作用机制以及它们的构效关系。
Inflammation is recently recognized as one of the hallmarks of human cancer. Chronic inflammatory response plays a critical role in cancer development, progression, metastasis, and resistance to chemotherapy. Conversely, the oncogenic aberrations also generate an inflammatory microenvironment, enabling the development and progression of cancer. The molecular mechanisms of action that are responsible for inflammatory cancer and cancer-associated inflammation are not fully understood due to the complex crosstalk between oncogenic and pro-inflammatory genes. However, molecular mediators that regulate both inflammation and cancer, such as NF-κB and STAT have been considered as promising targets for preventing and treating these diseases. Recent works have further demonstrated an important role of oncogenes (e.g., NFAT1, MDM2) and tumor suppressor genes (e.g., p53) in cancer-related inflammation. Natural products that target these molecular mediators have shown anticancer and anti-inflammatory activities in preclinical and clinical studies. Sesquiterpenoids (STs), a class of novel plant-derived secondary metabolites have attracted great interest in recent years because of their diversity in chemical structures and pharmacological activities. At present, we and other investigators have found that dimeric sesquiterpenoids (DSTs) may exert enhanced activity and binding affinity to molecular targets due to the increased number of alkylating centers and improved conformational flexibility and lipophilicity. Here, we focus our discussion on the activities and mechanisms of action of STs and DSTs in treating inflammation and cancer as well as their structure-activity relationships.