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棓丙酯的新作用:细胞毒性潜力及其在癌症治疗中的药物相关性。

Emerging role of plumbagin: Cytotoxic potential and pharmaceutical relevance towards cancer therapy.

机构信息

Cancer Drug Resistance Laboratory, Department of Life Science, National Institute of Technology Rourkela, 769008, Sundergarh, Odisha, India.

Cancer Drug Resistance Laboratory, Department of Life Science, National Institute of Technology Rourkela, 769008, Sundergarh, Odisha, India.

出版信息

Food Chem Toxicol. 2019 Mar;125:566-582. doi: 10.1016/j.fct.2019.01.018. Epub 2019 Jan 24.

Abstract

Plumbagin is a naphthoquinone derived yellow crystalline phytochemical. Plumbagin has a wide range of biological effects including cytotoxicity against cancer cells both in vitro and in vivo. Due to the pleiotropic nature of plumbagin, it shows the anticancer effect by targeting several molecular mechanisms including apoptosis and autophagic pathways, cell cycle arrest, anti-angiogenic pathways, anti-invasion and anti-metastasis pathways. Among many signaling pathways the key regulatory genes regulated by plumbagin are NF-kβ, STAT3, and AKT, etc. Plumbagin is also a potent inducer of ROS, suppressor of cellular glutathione, and causes DNA strand break by oxidative DNA base damages. In vivo studies suggested that plumbagin significantly reduces the tumor weight and volume in dose-dependent manner without any side effects in tested model organisms. Another exciting aspect of plumbagin is the ability to re-sensitize the chemo and radioresistant cancer cells when used in combination or alone. Nano encapsulation of plumbagin overcomes the poor water solubility and bioavailability obstacles, enhancing the pharmaceutical relevance with better therapeutic efficacy. Moreover, plumbagin can be introduced as a future phytotherapeutic anticancer drug after fully satisfied preclinical and clinical trials.

摘要

白花丹醌是一种萘醌类黄色结晶植物化学物质。白花丹醌具有广泛的生物学效应,包括体外和体内对癌细胞的细胞毒性。由于白花丹醌的多效性,它通过靶向多种分子机制,包括细胞凋亡和自噬途径、细胞周期停滞、抗血管生成途径、抗侵袭和抗转移途径,显示出抗癌作用。在许多信号通路中,白花丹醌调节的关键调控基因包括 NF-κB、STAT3 和 AKT 等。白花丹醌也是 ROS 的有效诱导剂,细胞谷胱甘肽的抑制剂,并通过氧化 DNA 碱基损伤导致 DNA 链断裂。体内研究表明,白花丹醌在测试的模型生物中以剂量依赖的方式显著降低肿瘤重量和体积,没有任何副作用。白花丹醌的另一个令人兴奋的方面是,当与化疗或放疗联合使用或单独使用时,它能够重新敏感化化疗和放疗耐药的癌细胞。白花丹醌的纳米封装克服了其水溶性和生物利用度差的障碍,提高了药物相关性,具有更好的治疗效果。此外,白花丹醌在充分满足临床前和临床试验后,可以作为一种未来的植物抗癌药物引入。

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