Montazeri Maryam, Sadeghizadeh Majid, Pilehvar-Soltanahmadi Yones, Zarghami Faraz, Khodi Samaneh, Mohaghegh Mina, Sadeghzadeh Hadi, Zarghami Nosratollah
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Int J Pharm. 2016 Jul 25;509(1-2):244-254. doi: 10.1016/j.ijpharm.2016.05.039. Epub 2016 May 24.
The side-effects observed in conventional therapies have made them unpromising in curing Hepatocellular carcinoma; therefore, developing novel treatments can be an overwhelming significance. One of such novel agents is curcumin which can induce apoptosis in various cancerous cells, however, its poor solubility is restricted its application. To overcome this issue, this paper employed dendrosomal curcumin (DNC) was employed to in prevent hepatocarcinoma in both RNA and protein levels. Hepatocarcinoma cells, p53 wild-type HepG2 and p53 mutant Huh7, were treated with DNC and investigated for toxicity study using MTT assay. Cell cycle distribution and apoptosis were analyzed using Flow-cytometry and Annexin-V-FLUOS/PI staining. Real-time PCR and Western blot were employed to analyze p53, BAX, Bcl-2, p21 and Noxa in DNC-treated cells. DNC inhibited the growth in the form of time-dependent manner, while the carrier alone was not toxic to the cell. Flow-cytometry data showed the constant concentration of 20μM DNC during the time significantly increases cell population in SubG1 phase. Annexin-V-PI test showed curcumin-induced apoptosis was enhanced in Huh7 as well as HepG2, compared to untreated cells. Followed by treatment, mRNA expression of p21, BAX, and Noxa increased, while the expression of Bcl-2 decreased, and unlike HepG2, Huh7 showed down-regulation of p53. In summary, DNC-treated hepatocellular carcinoma cells undergo apoptosis by changing the expression of genes involved in the apoptosis and proliferation processes. These findings suggest that DNC, as a plant-originated therapeutic agent, could be applied in cancer treatment.
传统疗法中观察到的副作用使其在治疗肝细胞癌方面前景不佳；因此，开发新的治疗方法具有极其重要的意义。姜黄素就是这样一种新型药物，它可以诱导多种癌细胞凋亡，然而，其溶解度低限制了它的应用。为了克服这个问题，本文采用树枝状姜黄素（DNC）在RNA和蛋白质水平上预防肝癌。用DNC处理肝癌细胞、p53野生型HepG2和p53突变型Huh7，并使用MTT法进行毒性研究。使用流式细胞术和膜联蛋白-V-荧光素/碘化丙啶染色分析细胞周期分布和凋亡情况。采用实时PCR和蛋白质印迹法分析DNC处理细胞中的p53、BAX、Bcl-2、p21和Noxa。DNC以时间依赖性方式抑制生长，而单独的载体对细胞无毒。流式细胞术数据显示，在这段时间内，20μM DNC的恒定浓度显著增加了亚G1期的细胞数量。膜联蛋白-V-碘化丙啶试验表明，与未处理的细胞相比，姜黄素诱导的凋亡在Huh7和HepG2中均增强。处理后，p21、BAX和Noxa的mRNA表达增加，而Bcl-2的表达降低，与HepG2不同，Huh7显示p53下调。总之，DNC处理的肝癌细胞通过改变参与凋亡和增殖过程的基因表达而发生凋亡。这些发现表明，DNC作为一种植物源治疗剂，可应用于癌症治疗。
