Limtrakul Pornngarm
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand.
Adv Exp Med Biol. 2007;595:269-300. doi: 10.1007/978-0-387-46401-5_12.
This overview presents curcumin as a significant chemosensitizer in cancer chemotherapy. Although the review focuses on curcumin and its analogues on multidrug resistance (MDR) reversal, the relevance of curcumin as a nuclear factor (NF)-KB blocker and sensitizer of many chemoresistant cancer cell lines to chemotherapeutic agents will also be discussed. One of the major mechanisms of MDR is the enhanced ability of tumor cells to actively efflux drugs, leading to a decrease in cellular drug accumulation below toxic levels. Active drug efflux is mediated by several members of the ATP-binding cassette (ABC) superfamily of membrane transporters, which have now been subdivided into seven families designated A through G. Among these ABC families, the classical MDR is attributed to the elevated expression of ABCB1 (Pgp), ABCC1 (MRP1), and ABCG2 (MXR). The clinical importance of Pgp, MRP1, and MXR for MDR and cancer treatment has led to the investigation of the inhibiting properties of several compounds on these transporters. At present, due in part to the disappointing results associated with the many side effects of synthetic modulators that have been used in clinical trials, current research efforts are directed toward the identification of novel compounds, with attention to dietary natural products. The advantage is that they exhibit little or virtually no side effects and do not further increase the patient's medication burden.
本综述介绍了姜黄素作为癌症化疗中一种重要的化学增敏剂的情况。尽管该综述聚焦于姜黄素及其类似物对多药耐药性(MDR)的逆转作用,但也将讨论姜黄素作为核因子(NF)-κB阻断剂以及许多化疗耐药癌细胞系对化疗药物的增敏剂的相关性。MDR的主要机制之一是肿瘤细胞主动外排药物的能力增强,导致细胞内药物积累降至毒性水平以下。主动药物外排由膜转运蛋白ATP结合盒(ABC)超家族的几个成员介导,目前已细分为七个家族,分别命名为A至G。在这些ABC家族中,经典的MDR归因于ABCB1(Pgp)、ABCC1(MRP1)和ABCG2(MXR)的表达升高。Pgp、MRP1和MXR对MDR及癌症治疗的临床重要性引发了对几种化合物对这些转运蛋白抑制特性的研究。目前,部分由于与临床试验中使用的合成调节剂的许多副作用相关的令人失望的结果,当前的研究工作致力于鉴定新型化合物,同时关注膳食天然产物。其优势在于它们几乎没有或实际上没有副作用,并且不会进一步增加患者的用药负担。