Hematology and Hemotherapy Center, University of Campinas, HEMOCENTRO UNICAMP, Campinas, São Paulo, Brazil.
Faculty of Pharmaceutical Science, University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.
Cancer Chemother Pharmacol. 2021 Jan;87(1):1-22. doi: 10.1007/s00280-020-04170-5. Epub 2020 Nov 3.
Qinghaosu, known as artemisinin (ARS), has been for over two millennia, one of the most common herbs prescribed in traditional Chinese medicine (TCM). ARS was developed as an antimalarial drug and currently belongs to the established standard treatments of malaria as a combination therapy worldwide. In addition to the antimalarial bioactivity of ARS, anticancer activities have been shown both in vitro and in vivo. Like other natural products, ARS acts in a multi-specific manner also against hematological malignancies. The chemical structure of ARS is a sesquiterpene lactone, which contains an endoperoxide bridge essential for activity. The main mechanism of action of ARS and its derivatives (artesunate, dihydroartemisinin, artemether) toward leukemia, multiple myeloma, and lymphoma cells comprises oxidative stress response, inhibition of proliferation, induction of various types of cell death as apoptosis, autophagy, ferroptosis, inhibition of angiogenesis, and signal transducers, as NF-κB, MYC, amongst others. Therefore, new pharmaceutically active compounds, dimers, trimers, and hybrid molecules, could enhance the existing therapeutic alternatives in combating hematologic malignancies. Owing to the high potency and good tolerance without side effects of ARS-type drugs, combination therapies with standard chemotherapies could be applied in the future after further clinical trials in hematological malignancies.
青蒿素（ARS），又称青蒿素，在过去的两千多年里，一直是中药（TCM）中最常用的草药之一。ARS 已被开发为一种抗疟药物，目前作为联合疗法在全球范围内被列为疟疾的既定标准治疗方法之一。除了 ARS 的抗疟生物活性外，它在体外和体内都显示出抗癌活性。与其他天然产物一样，ARS 也以多特异性方式作用于血液系统恶性肿瘤。ARS 的化学结构是一种倍半萜内酯，其中包含一个对活性至关重要的内过氧化物桥。ARS 及其衍生物（青蒿琥酯、二氢青蒿素、蒿甲醚）对白血病、多发性骨髓瘤和淋巴瘤细胞的主要作用机制包括氧化应激反应、抑制增殖、诱导各种类型的细胞死亡，如细胞凋亡、自噬、铁死亡、抑制血管生成和信号转导，如 NF-κB、MYC 等。因此，新的药用活性化合物、二聚体、三聚体和杂合分子，可以增强现有治疗血液系统恶性肿瘤的替代方法。由于 ARS 类药物具有高疗效和良好的耐受性，没有副作用，因此在未来经过进一步的临床试验后，可能会与标准化疗联合应用于血液系统恶性肿瘤。
