Nag Sayoni, Manna Krishnendu, Saha Krishna Das
Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology 4 Raja S.C. Mullick Road Kolkata-700032 West Bengal India
RSC Adv. 2019 Mar 11;9(14):8025-8038. doi: 10.1039/c9ra00808j. eCollection 2019 Mar 6.
Gold nanoparticle formulated tannic acid (AuNP-TA) was synthesized, and its anticancer activity was compared to that of free tannic acid (TA). The half maximal inhibitory concentration (IC) was reduced by half when cell lines were treated with AuNP-TA as compared to IC values upon free TA treatment. Both showed better cytotoxic activity in HCT116 cell line as compared to MCF7 and HepG2. AuNP-TA induced death of HCT116 cells was associated with characteristic apoptotic changes. At the same treatment dose, AuNP-TA generated more ROS, caused a more extensive DNA damage and promoted higher expression of p53 and p21 than TA. Treatment with AuNP-TA regulated generation of p53 and ROS bi-directionally. Binding studies showed that TA lowered the expression of Akt, which inhibited the survival of colon cancer cells. Also, cell cycle arrest at the G2/M phase, enhanced expression of caspase-3/9, Bak, and Bax, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome were observed in AuNP-TA treated HCT116 cells. Thus, AuNP-TA is more efficient than TA in inducing apoptotic cell death of HCT116 cells the ROS/P53/Akt axis.
合成了金纳米颗粒包载的单宁酸（AuNP-TA），并将其抗癌活性与游离单宁酸（TA）的抗癌活性进行了比较。与游离TA处理后的IC值相比，用AuNP-TA处理细胞系时，半数最大抑制浓度（IC）降低了一半。与MCF7和HepG2相比，两者在HCT116细胞系中均表现出更好的细胞毒性活性。AuNP-TA诱导的HCT116细胞死亡与典型的凋亡变化有关。在相同的处理剂量下，AuNP-TA比TA产生更多的活性氧（ROS），导致更广泛的DNA损伤，并促进p53和p21的更高表达。用AuNP-TA处理双向调节p53和ROS的生成。结合研究表明，TA降低了Akt的表达，从而抑制了结肠癌细胞的存活。此外，在AuNP-TA处理的HCT116细胞中观察到细胞周期阻滞于G2/M期、caspase-3/9、Bak和Bax的表达增强、线粒体膜电位丧失以及胞质细胞色素水平升高。因此，在通过ROS/P53/Akt轴诱导HCT116细胞凋亡性细胞死亡方面，AuNP-TA比TA更有效。
