靛玉红衍生物7-溴靛玉红-3'-肟（7BIO）诱导甲状腺癌细胞发生非典型细胞死亡
Induction of atypical cell death in thyroid carcinoma cells by the indirubin derivative 7-bromoindirubin-3'-oxime (7BIO).
作者信息
Broecker-Preuss Martina, Becher-Boveleth Nina, Gall Susanne, Rehmann Katrin, Schenke Susann, Mann Klaus
机构信息
Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany ; Department of Clinical Chemistry, University Hospital Essen, Hufelandstr. 55, Essen, Germany.
Division of Laboratory Research, Department of Endocrinology and Metabolism, University Hospital Essen, Hufelandstr. 55, Essen, Germany ; Clinic of Nuclear Medicine, University Hospital Essen, Hufelandstr. 55, Essen, Germany.
出版信息
Cancer Cell Int. 2015 Oct 12;15:97. doi: 10.1186/s12935-015-0251-8. eCollection 2015.
BACKGROUND
The indirubin derivative 7-bromoindirubin-3'-oxime (7BIO) has already shown anticancer properties by causing cell death in some tumour cell lines and may be a new therapeutic option for treatment-resistant tumour cells. Since dedifferentiated and anaplastic thyroid carcinomas do not take up radioiodine and are insensitive to chemotherapeutic treatment and external radiation, direct cell death induction in these tumour cells may be a promising approach. We thus investigated the effect of 7BIO on thyroid carcinoma cell lines of different histological origins and characterized the type of cell death induction by 7BIO.
METHODS
Cell viability was measured with MTT assay. Cell death was analysed by caspase 3/7 activity, lactate dehydrogenase liberation, caspase cleavage products, DNA fragmentation, cell cycle phase distribution and LC3B analysis.
RESULTS
After 7BIO treatment, cell viability was reduced in all 14 thyroid carcinoma cell lines investigated. Treated cells showed DNA fragmentation, cell cycle arrest and lactate dehydrogenase liberation but no LC3B cleavage. Caspase activation following 7BIO treatment was found in five of six cell lines investigated. Interestingly, inhibition of caspases had no effect on viability of the cells after 7BIO incubation.
CONCLUSIONS
Our results indicate that 7BIO efficiently killed dedifferentiated thyroid carcinoma cells. It induced a non-classical kind of cell death that was caspase-independent and includes DNA fragmentation. 7BIO and related indirubin components thus may have value as a new therapeutic option for dedifferentiated thyroid cancer irrespective of the exact target molecules and the kind of cell death they induce.
背景
靛玉红衍生物7-溴靛玉红-3'-肟（7BIO）已通过在某些肿瘤细胞系中诱导细胞死亡显示出抗癌特性，可能是治疗耐药肿瘤细胞的一种新的治疗选择。由于去分化型和间变性甲状腺癌不摄取放射性碘，对化疗和外照射不敏感，在这些肿瘤细胞中直接诱导细胞死亡可能是一种有前景的方法。因此，我们研究了7BIO对不同组织学来源的甲状腺癌细胞系的影响，并对7BIO诱导的细胞死亡类型进行了表征。
方法
用MTT法测定细胞活力。通过半胱天冬酶3/7活性、乳酸脱氢酶释放、半胱天冬酶裂解产物、DNA片段化、细胞周期阶段分布和LC3B分析来分析细胞死亡情况。
结果
7BIO处理后，在所研究的所有14种甲状腺癌细胞系中细胞活力均降低。处理后的细胞表现出DNA片段化、细胞周期停滞和乳酸脱氢酶释放，但没有LC3B裂解。在所研究的6种细胞系中的5种中发现了7BIO处理后半胱天冬酶的激活。有趣的是，半胱天冬酶的抑制对7BIO孵育后细胞的活力没有影响。
结论
我们的结果表明，7BIO能有效杀死去分化型甲状腺癌细胞。它诱导了一种非经典的细胞死亡，这种细胞死亡不依赖半胱天冬酶，包括DNA片段化。因此，7BIO和相关的靛玉红成分可能作为去分化型甲状腺癌的一种新的治疗选择具有价值，而不论其确切的靶分子以及它们诱导的细胞死亡类型如何。
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