摘要
通过对Ridaifen-G(RID-G)诱导造血细胞U937、Raji、THP-1和IM-9死亡是否需要Z-VAD-fmk(一种细胞凋亡蛋白酶抑制剂)的研究,发现RID-G以细胞凋亡蛋白酶非依存性的方式诱导细胞死亡,并伴随有线粒体功能紊乱。Z-VAD-fmk对U937细胞的死亡没有影响,但抑制etoposide诱导的细胞凋亡;DNA片段化结果表明,RID-G可破坏Raji和THP-1细胞的DNA,经RID-G处理后的U937细胞的DNA条带没有经etoposide处理的清晰。此外,Z-VAD-fmk对U937、THP-1和Raji细胞DNA的片段化程度有不同的影响,抑制细胞死亡。这些结果表明,RID-G诱导的非典型细胞死亡不依赖于caspase,且伴随有线粒体功能紊乱。
We have investigated antitumor activities of Ridaifens （RIDs）, which are a series of synthesized Tamoxifen （TAM） derivatives. In this study, we focused on one of RIDs, Ridaifen-G （RID-G）, and investigated the cell death-inducing activity of it in four neoplastic hematopoietic cell lines, U937, Raji, THP-1, and IM-9 cells in the presence or absence of a pan-caspase inhibitor, Z-VAD-fmk. The aim of this study is to characterize the mode of RID-G-induced cell death, as compared with a typical apoptosis of etoposide-treated U937 cells, which die mainly through mitochondria-mediated apoptotic pathway in a caspase-dependent manner. To obtain reliable results, we analyzed RID-G-induced cell death by four methods, i.e., MTT assay, MitoTracker staining, AnnexinV-FITC/Propidium Iodide double staining, and DNA ladder formation. These analyses revealed that RID-G-induced cell death is accompanied by mitochondrial dysfunction and executed in a caspase-independent manner except DNA ladder formation. Z-VAD-fmk did not suppress the death, but suppressed etoposide-induced apoptosis in U937 cells. In DNA ladder formation analysis, RID-G induced a smear of DNA fragmentation in Raji and THP-1 cells, and RID- G-treated U937 cells showed less DNA ladder formation than when treated with etoposide. In addition, Z-VAD-fmk showed different effects on these DNA fragmentations： it largely suppressed, partialy suppressed, and on the contrary, enhanced DNA fragmentaion in U937, THP-1, and Raji cells, respectively. These results suggest that RID-G induces caspase-independent atypical cell death, which is accompanied bv mitochondrial dysfunction.
出处
《中国细胞生物学学报》
CAS
CSCD
2011年第6期635-644,共10页
Chinese Journal of Cell Biology
