Liu Jia-Jun, Lin Dong-Jun, Liu Pei-Qing, Huang Min, Li Xu-Dong, Huang Ren-Wei
Department of Hematology and Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, P.R. China.
J Biomed Sci. 2006 Nov;13(6):813-23. doi: 10.1007/s11373-006-9110-x. Epub 2006 Sep 6.
Tanshinone IIA, a diterpene quinone extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, is used widely and successfully in clinics in China for treating inflammatory diseases. Recently tanshinone IIA has been reported to have apoptosis inducing effects on a large variety of cancer cells. In this study, the anti-proliferation and apoptosis inducing effects of tanshinone IIA as well as its influence on cell adhesion to and invasion through the extracellular matrix (ECM) on acute promyelocytic leukemia (APL) NB4 cells in vitro were studied. Cell proliferation was assessed by MTT assay, cell apoptosis was observed by Hoechst 33258 staining and flow cytometry (FCM); The variation of caspase-3 and apoptotic related genes were assayed by Western blotting, cell mitochondrial membrane potential as well as cell adhesive and invasive effects were also investigated by using standard methods. The results showed that tanshinone IIA exhibited induction of apoptosis by activation of caspase-3, downregulation of anti-apoptotic protein bcl-2 and bcl-xl and upregulation of pro-apoptotic protein bax, as well as disruption of the mitochondrial membrane potential. Furthermore, treatment by tanshinone IIA could reduce cell adhesion to and invasion through ECM in leukemia NB4 cells. These data provide a potential mechanism for tanshinone IIA-induced apoptosis and cell growth inhibition in leukemia NB4 cells, suggesting that tanshinone IIA may serve as an effective adjunctive reagent for the treatment of APL.
丹参酮IIA是从传统草药丹参中提取的一种二萜醌，在中国临床上被广泛且成功地用于治疗炎症性疾病。最近有报道称丹参酮IIA对多种癌细胞具有诱导凋亡的作用。在本研究中，对丹参酮IIA在体外对急性早幼粒细胞白血病（APL）NB4细胞的抗增殖和诱导凋亡作用及其对细胞黏附于细胞外基质（ECM）和穿过ECM侵袭的影响进行了研究。通过MTT法评估细胞增殖，通过Hoechst 33258染色和流式细胞术（FCM）观察细胞凋亡；通过蛋白质免疫印迹法检测caspase-3和凋亡相关基因的变化，同时采用标准方法研究细胞线粒体膜电位以及细胞黏附和侵袭作用。结果表明，丹参酮IIA通过激活caspase-3、下调抗凋亡蛋白bcl-2和bcl-xl以及上调促凋亡蛋白bax来诱导凋亡，同时破坏线粒体膜电位。此外，丹参酮IIA处理可降低白血病NB4细胞对ECM的黏附和穿过ECM的侵袭。这些数据为丹参酮IIA诱导白血病NB4细胞凋亡和抑制细胞生长提供了潜在机制，表明丹参酮IIA可能作为治疗APL的有效辅助试剂。
