Chen Zhi-chao, Li Qiu-bai, Shao Jing, Lü Jian, You Yong, Zhong Zhao-dong, Zou Ping
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhonghua Yi Xue Za Zhi. 2006 Jul 25;86(28):1993-6.
To investigate the effect of parthenolide (PTL) on human multiple myeloma (MM) cells in vitro and its mechanism.
Human MM cells of the line PRMI8266 were cultured and treated with PTL of the concentrations of 1, 2.5, 5, 7.5, and 10 micromol/L for 24, 48, or 72 hours. MM cells treated with DMSO were used as control group. The optical density was measured so as to draw a growth curve. The cell viability was detected by MTT and trypan-blue exclusion. The apoptosis was detected by flow cytometry. AO/EB staining and Wright-Giemsa staining were used to observe the morphological changes of the cells by fluorescence microscope and light microscope respectively. The caspase-3 activity was evaluated by BD ApoAlert Caspase Colorimetric Assay Kit.
PTL significantly inhibited the proliferation and viability of the MM cells time and dose-dependently (all P < 0.01), and significantly induced the cell apoptosis after 48 h in a dose-dependent manner (P < 0.01). The early cell apoptosis rates for PTL of the concentrations of 2, 5 and 10 micromol/L were 17.1% +/- 2.6%, 33.6% +/- 3.8%, and 40.9% +/- 3.1% respectively, all significantly higher than that of the control group (5.6% +/- 1.2%, all P < 0.01). The MM cells treated with PTL of the concentration of 5 micromol/L for 48 h showed typical cell apoptotic features. The caspase-3 activity of the MM cells was enhanced significantly by PTL in a time and dose-dependent manner (all P < 0.01).
This first report of anti-proliferation and apoptosis induction effects of PTL on MM cells shows that able to significantly inhibit the proliferation and induce the apoptosis of MM cells and enhance the caspase-3 activity, PTL may be a potentially useful drug for treatment of MM.
研究小白菊内酯（PTL）对人多发性骨髓瘤（MM）细胞的体外作用及其机制。
培养人PRMI8266骨髓瘤细胞系，分别用浓度为1、2.5、5、7.5和10 μmol/L的PTL处理24、48或72小时。用二甲基亚砜（DMSO）处理的MM细胞作为对照组。测量光密度以绘制生长曲线。采用MTT法和台盼蓝拒染法检测细胞活力。通过流式细胞术检测细胞凋亡。分别用AO/EB染色和瑞氏-吉姆萨染色，通过荧光显微镜和光学显微镜观察细胞的形态变化。用BD ApoAlert Caspase比色分析试剂盒评估caspase-3活性。
PTL能显著抑制MM细胞的增殖和活力，呈时间和剂量依赖性（均P < 0.01），并在48小时后显著诱导细胞凋亡，呈剂量依赖性（P < 0.01）。浓度为2、5和10 μmol/L的PTL处理后早期细胞凋亡率分别为17.1%±2.6%、33.6%±3.8%和40.9%±3.1%，均显著高于对照组（5.6%±-1.2%，均P < 0.01）。用5 μmol/L的PTL处理48小时的MM细胞呈现典型的细胞凋亡特征。PTL能显著增强MM细胞的caspase-3活性，呈时间和剂量依赖性（均P < 0.01）。
PTL对MM细胞抗增殖和诱导凋亡作用的首次报道表明，PTL能显著抑制MM细胞增殖、诱导凋亡并增强caspase-3活性，可能是治疗MM的潜在有效药物。
