Gu Guiying, Qi Huanhuan, Jiang Tianyue, Ma Bo, Fang Zheng, Xu Hong, Zhang Qi
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, Jiangsu 210009, P.R. China.
School of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, Jiangsu 210009, P.R. China.
Oncol Lett. 2017 Mar;13(3):1365-1369. doi: 10.3892/ol.2017.5588. Epub 2017 Jan 11.
Raddeanin A, one of the triterpenoid saponins extracted from rhizome of the Ranunculaceae family, has demonstrated the ability to inhibit the growth of human hepatic and gastric cancer cells. However, the effects of Raddeanin A on human colon cancer cells have not been investigated extensively. The present study aimed to examine the antiproliferative and apoptosis-inducing effects of Raddeanin A on the HCT-116 human colon cancer cell line , and evaluate the pharmacokinetic and biodistribution properties of Raddeanin A in mice following a single oral administration. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess the cytotoxicity of Raddeanin A against HCT-116 cells. 4',6-Diamidino-2-phenylindole, dihydrochloride staining and flow cytometry were performed to further examine the apoptosis-inducing capability of Raddeanin A. The concentrations of Raddeanin A in the plasma and tissues were analyzed using liquid chromatography-tandem mass spectrometry. Raddeanin A showed a dose-dependent antiproliferative effect towards the HCT-116 cells, with a half maximal inhibitory concentration of ~1.4 µM. Treatment with Raddeanin A resulted in a significant induction of apoptosis, observed as apparent morphological changes of the nuclei, with a total apoptotic ratio of 41.8% at a concentration of 3 µM. Low concentrations of Raddeanin A were detected in the heart, liver, spleen, lung, kidney and plasma of the mice following oral administration, however, the majority of the Raddeanin A was distributed in the intestinal tract, particularly in the colon and caecum. These present study confirmed the growth-inhibitory and apoptosis-inducing effects of Raddeanin A on HCT-116 cells and performed preliminary examinations of its pharmacokinetic properties, which provide a foundation for further investigating the inhibitory mechanism on the colon cancer cells .
鸦胆子素A是从毛茛科植物根茎中提取的三萜皂苷之一，已证明具有抑制人肝癌细胞和胃癌细胞生长的能力。然而，鸦胆子素A对人结肠癌细胞的作用尚未得到广泛研究。本研究旨在探讨鸦胆子素A对HCT - 116人结肠癌细胞系的抗增殖和诱导凋亡作用，并评估单次口服给药后鸦胆子素A在小鼠体内的药代动力学和生物分布特性。采用3-(4,5 - 二甲基噻唑 - 2 - 基)-2,5 - 二苯基四氮唑溴盐法评估鸦胆子素A对HCT - 116细胞的细胞毒性。进行4',6 - 二脒基 - 2 - 苯基吲哚二盐酸盐染色和流式细胞术以进一步检测鸦胆子素A的诱导凋亡能力。使用液相色谱 - 串联质谱法分析血浆和组织中鸦胆子素A的浓度。鸦胆子素A对HCT - 116细胞呈现剂量依赖性抗增殖作用，半数最大抑制浓度约为1.4 μM。鸦胆子素A处理导致明显的凋亡诱导，表现为细胞核明显的形态变化，在浓度为3 μM时总凋亡率为41.8%。口服给药后，在小鼠的心脏、肝脏、脾脏、肺脏、肾脏和血浆中检测到低浓度的鸦胆子素A，然而，大部分鸦胆子素A分布在肠道，特别是结肠和盲肠。本研究证实了鸦胆子素A对HCT - 116细胞的生长抑制和诱导凋亡作用，并对其药代动力学特性进行了初步研究，为进一步研究其对结肠癌细胞的抑制机制提供了基础。
