Anticancer Effect of AntiMalarial Artemisinin Compounds.
Anticancer Effect of AntiMalarial Artemisinin Compounds.
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DOI：
10.4103/2141-9248.153609
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发表时间：
2015-03
影响因子：
--
通讯作者：
Das AK
中科院分区：
文献类型：
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作者：
Das AK
抗疟疾药物青蒿素已在体外和动物实验中显示出抗癌活性，但在人类癌症方面的经验却很少。然而，青蒿素通过多种分子机制杀死癌细胞的能力已被探索。 PubMed 检索了大约 127 篇关于抗疟药的抗癌作用的论文，结果显示此类药物（包括其他抗疟药）具有多种生物学特性，其中包括抗癌特性。实验证据表明，青蒿素化合物可能是治疗快速扩散的高度侵袭性癌症的替代疗法，且不会产生耐药性。它们还表现出与其他抗癌药物的协同作用，且不会增加对正常细胞的毒性。研究发现，半合成青蒿素衍生物通过细胞凋亡、G0/G1 细胞周期停滞和氧化应激等机制，比单体青蒿素衍生物具有更高的抗肿瘤活性。这些抗癌作用的确切激活机制和分子基础尚未完全阐明。青蒿素似乎调节核因子-κ B、生存素、NOXA、缺氧诱导因子-1α和BMI-1等关键因子，涉及可能影响正常细胞的药物反应、药物相互作用、耐药性和相关参数的多种途径。较新的合成青蒿素已被开发出来，显示出显着的抗肿瘤活性，但有关这些合成化合物的作用方式的信息仍然有限。鉴于新出现的数据，需要在不同的癌细胞及其表型中进一步研究与已建立的化疗的特定相互作用，并使用不同的半合成和合成青蒿素衍生物进一步验证。
The anti-malarial drug artemisinin has shown anticancer activity in vitro and animal experiments, but experience in human cancer is scarce. However, the ability of artemisinins to kill cancer cells through a variety of molecular mechanisms has been explored. A PubMed search of about 127 papers on anti-cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. Experimental evidences suggest that artemisinin compounds may be a therapeutic alternative in highly aggressive cancers with rapid dissemination, without developing drug resistance. They also exhibit synergism with other anticancer drugs with no increased toxicity toward normal cells. It has been found that semisynthetic artemisinin derivatives have much higher antitumor activity than their monomeric counterparts via mechanisms like apoptosis, arrest of cell cycle at G0/G1, and oxidative stress. The exact mechanism of activation and molecular basis of these anticancer effects are not fully elucidated. Artemisinins seem to regulate key factors such as nuclear factor-kappa B, survivin, NOXA, hypoxia-inducible factor-1α, and BMI-1, involving multiple pathways that may affect drug response, drug interactions, drug resistance, and associated parameters upon normal cells. Newer synthetic artemisinins have been developed showing substantial antineoplastic activity, but there is still limited information regarding the mode of action of these synthetic compounds. In view of the emerging data, specific interactions with established chemotherapy need to be further investigated in different cancer cells and their phenotypes and validated further using different semisynthetic and synthetic artemisinin derivatives.