Cytotoxicity of Salvia miltiorrhiza Against Multidrug-Resistant Cancer Cells.
Cytotoxicity of Salvia miltiorrhiza Against Multidrug-Resistant Cancer Cells.
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DOI：
10.1142/s0192415x16500488
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Ching‐Fen Wu;Stefan Bohnert;E. Thines;T. Efferth
中科院分区：
文献类型：
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作者：
Ching‐Fen Wu;Stefan Bohnert;E. Thines;T. Efferth
丹参（Lamiaceae）是一种著名的中药，具有多种治疗活性，包括抗癌作用。本研究研究了丹参（SM）根提取物对多种耐药和敏感癌细胞的细胞毒性及其生物学机制。CEM/ADR5000细胞对CCRF-CEM细胞的耐药率为1.68倍，而HCT116 (p53[公式：见文]和U87。与亲本细胞相比，EGFR细胞是超敏的（侧敏的）。SM根提取物刺激ROS生成、细胞周期S期阻滞和细胞凋亡。通过增加caspase 3,7,9和聚adp核糖聚合酶（PARP）的裂解，证实了诱导内在凋亡途径的有效性。SM处理后，MAP激酶JNK、ERK1/2和p38明显磷酸化，核P65下调。全转录组比较分析显示，不同功能编码基因的表达与细胞对隐丹参酮（SM根提取物的主要成分之一）的应答有关。综上所述，SM根提取物对多种敏感和耐药的癌细胞具有深刻的细胞毒性，并诱导了内在的凋亡途径。
Salvia miltiorrhiza Bunge (Lamiaceae) is a well-known Chinese herb that possesses numerous therapeutic activities, including anticancer effects. In this study, the cytotoxicity and the biological mechanisms of S. miltiorrhiza (SM) root extract on diverse resistant and sensitive cancer cell lines were investigated. CEM/ADR5000 cells were 1.68-fold resistant to CCRF-CEM cells, while HCT116 (p53[Formula: see text] and U87.MG[Formula: see text]EGFR cells were hypersensitive (collateral sensitive) compared to their parental cells. SM root extract stimulated ROS generation, cell cycle S phase arrest and apoptosis. The induction of the intrinsic apoptotic pathway was validated by increased cleavage of caspase 3, 7, 9 and poly ADP-ribose polymerase (PARP). MAP kinases including JNK, ERK1/2 and p38 were obviously phosphorylated and nuclear P65 was downregulated upon SM treatment. Transcriptome-wide COMPARE analysis revealed that the expression of encoding genes with diverse functions were associated with the cellular response to cryptotanshinone, one of the main constituents of SM root extract. In conclusion, SM root extract exerted profound cytotoxicity towards various sensitive and resistant cancer cells and induced the intrinsic apoptotic pathway.