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Repurposing of plant alkaloids for cancer therapy: Pharmacology and toxicology
Seminars in Cancer Biology ( IF 12.1 ) Pub Date : 2019-12-26 , DOI: 10.1016/j.semcancer.2019.12.010
Thomas Efferth 1 , Franz Oesch 2
Affiliation  

Drug repurposing (or repositioning) is an emerging concept to use old drugs for new treatment indications. Phytochemicals isolated from medicinal plants have been largely neglected in this context, although their pharmacological activities have been well investigated in the past, and they may have considerable potentials for repositioning. A grand number of plant alkaloids inhibit syngeneic or xenograft tumor growth in vivo. Molecular modes of action in cancer cells include induction of cell cycle arrest, intrinsic and extrinsic apoptosis, autophagy, inhibition of angiogenesis and glycolysis, stress and anti-inflammatory responses, regulation of immune functions, cellular differentiation, and inhibition of invasion and metastasis. Numerous underlying signaling processes are affected by plant alkaloids. Furthermore, plant alkaloids suppress carcinogenesis, indicating chemopreventive properties. Some plant alkaloids reveal toxicities such as hepato-, nephro- or genotoxicity, which disqualifies them for repositioning purposes. Others even protect from hepatotoxicity or cardiotoxicity of xenobiotics and established anticancer drugs. The present survey of the published literature clearly demonstrates that plant alkaloids have the potential for repositioning in cancer therapy. Exploitation of the chemical diversity of natural alkaloids may enrich the candidate pool of compounds for cancer chemotherapy and –prevention. Their further preclinical and clinical development should follow the same stringent rules as for any other synthetic drug as well. Prospective randomized, placebo-controlled clinical phase I and II trials should be initiated to unravel the full potential of plant alkaloids for drug repositioning.



中文翻译:

将植物生物碱重新用于癌症治疗:药理学和毒理学

药物再利用(或重新定位)是将旧药用于新的治疗适应症的新兴概念。在这种情况下,从药用植物中分离出的植物化学物质在很大程度上被忽视了,尽管它们的药理活性在过去已经得到了很好的研究,并且它们可能具有相当大的重新定位潜力。大量植物生物碱在体内抑制同基因或异种移植肿瘤的生长. 癌细胞中的分子作用模式包括诱导细胞周期停滞、内在和外在细胞凋亡、自噬、抑制血管生成和糖酵解、应激和抗炎反应、调​​节免疫功能、细胞分化以及抑制侵袭和转移。许多潜在的信号传导过程受到植物生物碱的影响。此外,植物生物碱可抑制致癌作用,表明具有化学预防特性。一些植物生物碱具有毒性,例如肝毒性、肾毒性或遗传毒性,这使它们失去了重新定位的资格。其他人甚至可以防止异生素和已建立的抗癌药物的肝毒性或心脏毒性。目前对已发表文献的调查清楚地表明植物生物碱具有在癌症治疗中重新定位的潜力。开发天然生物碱的化学多样性可能会丰富用于癌症化疗和预防的候选化合物库。他们进一步的临床前和临床开发也应遵循与任何其他合成药物相同的严格规则。应启动前瞻性随机、安慰剂对照临床 I 期和 II 期试验,以揭示植物生物碱在药物重新定位方面的全部潜力。他们进一步的临床前和临床开发也应遵循与任何其他合成药物相同的严格规则。应启动前瞻性随机、安慰剂对照临床 I 期和 II 期试验,以揭示植物生物碱在药物重新定位方面的全部潜力。他们进一步的临床前和临床开发也应遵循与任何其他合成药物相同的严格规则。应启动前瞻性随机、安慰剂对照临床 I 期和 II 期试验,以揭示植物生物碱在药物重新定位方面的全部潜力。

更新日期:2019-12-26
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