Quispe-Soto Edgar Teddy, Calaf Gloria M
Instituto de Alta Investigación, Universidad de Tarapacá, Arica 8097877, Chile.
Int J Oncol. 2016 Dec;49(6):2569-2577. doi: 10.3892/ijo.2016.3741. Epub 2016 Oct 19.
Global cancer burden increased to 14.1 million new cases in 2012; and breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012. Curcumin is the major bioactive ingredient extracted from the rhizome of the plant Curcuma longa (turmeric). Paclitaxel is a microtubule-stabilizing agent originally isolated from the bark of Taxus brevifolia. Curcumin and paclitaxel were evaluated with two human breast cancer cell lines as the luminal MCF-7 and the basal-like MDA-MB-231 that are either positive or negative for hormonal receptors estrogen receptor, progesterone receptor and HER2, respectively. Results indicated that curcumin combined with paclitaxel decreased c-Ha-Ras, Rho-A, p53 and Bcl-xL gene expression in comparison to control and substances alone in MCF-7 cell line. These two substances alone and combined decreased gene expression of Bcl-2 and NF-κB. However, CCND1 increased when both substances were combined in MCF-7 cells. Such substances decreased Bcl-2 and increased Bax protein expression. However, curcumin alone decreased IκBα and Stat-3 gene expression. Paclitaxel alone and combined increased IκBα and Stat-3. Curcumin alone and combined with paclitaxel increased p53, Bid, caspase-3, caspase-8 and Bax gene expression in MDA-MB-231, whereas Bcl-xL decreased such expression in MDA-MB-231 cells. When paclitaxel and curcumin were combined the expression of Bcl-2 protein was decreased. However, either substance alone and combined increased Bax protein expression corroborating the apoptotic effect of these substances. It can be concluded that curcumin may be of considerable value in synergistic therapy of breast cancer reducing the associated toxicity with use of drugs.
2012年,全球癌症负担增加至1410万例新发病例;乳腺癌是全球女性中最常见的癌症,2012年有近170万例新发病例被诊断出来。姜黄素是从植物姜黄(Curcuma longa)的根茎中提取的主要生物活性成分。紫杉醇是一种微管稳定剂,最初从短叶红豆杉的树皮中分离出来。使用两种人乳腺癌细胞系,即激素受体雌激素受体、孕激素受体和HER2分别为阳性或阴性的管腔型MCF-7和基底样MDA-MB-231,对姜黄素和紫杉醇进行了评估。结果表明,与对照组和单独使用药物相比,姜黄素与紫杉醇联合使用可降低MCF-7细胞系中c-Ha-Ras、Rho-A、p53和Bcl-xL基因的表达。这两种药物单独使用和联合使用均降低了Bcl-2和NF-κB的基因表达。然而,在MCF-7细胞中两种药物联合使用时,CCND1增加。这些药物降低了Bcl-2并增加了Bax蛋白的表达。然而,单独使用姜黄素可降低IκBα和Stat-3基因的表达。单独使用紫杉醇以及联合使用时均增加了IκBα和Stat-3。单独使用姜黄素以及与紫杉醇联合使用均增加了MDA-MB-231中p53、Bid、caspase-3、caspase-8和Bax基因的表达,而Bcl-xL在MDA-MB-231细胞中降低了这种表达。当紫杉醇和姜黄素联合使用时,Bcl-2蛋白的表达降低。然而,单独使用任何一种药物以及联合使用时均增加了Bax蛋白的表达,证实了这些药物的凋亡作用。可以得出结论,姜黄素在乳腺癌的协同治疗中可能具有相当大的价值,可降低药物使用的相关毒性。