白花丹素触发人乳腺癌细胞的 DNA 损伤反应、端粒功能障碍和基因组不稳定性。
Plumbagin triggers DNA damage response, telomere dysfunction and genome instability of human breast cancer cells.
机构信息
Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Tembusu College, National University of Singapore, Singapore.
出版信息
Biomed Pharmacother. 2016 Aug;82:256-68. doi: 10.1016/j.biopha.2016.05.007. Epub 2016 May 14.
AIM
Natural plant products are increasingly being used in cancer therapeutic studies due to their reduced normal cell toxicity. In this study, the anti-cancer properties of plumbagin, a naphthoquinone derivative extracted from the roots of Plumbago, were evaluated in breast cancer cells.
METHODS
To evaluate the effects of plumbagin on breast cancer cell types, we employed a variety of techniques comprising cell viability, cell cycle assay, comet assay, western blotting, immunocytochemistry, measurement of telomerase activity, telomere restriction fragment length, quantitative fluorescence in situ hybridisation, along with gene expression analysis of untreated cells.
RESULTS
Plumbagin treatment induced cytotoxicity in human breast cancer cells along with cell cycle arrest, DNA damage and cell death leading to apoptosis. Plumbagin was also found to suppress the telomerase activity in cancer cells accompanied by telomere attrition. Telomere shortening was corroborated by reduced telomere fluorescence on chromosome ends and genome instability.
CONCLUSION
Together, these findings may suggest the application of plumbagin as adjuvant modality in breast cancer therapeutics.
目的
由于天然植物产物对正常细胞的毒性较低，因此越来越多地被用于癌症治疗研究。本研究评估了从白花丹根部分离得到的萘醌衍生物白花丹醌对乳腺癌细胞的抗癌特性。
方法
为了评估白花丹醌对乳腺癌细胞类型的影响，我们采用了多种技术，包括细胞活力、细胞周期分析、彗星试验、western blot、免疫细胞化学、端粒酶活性测定、端粒限制性片段长度、定量荧光原位杂交以及未经处理细胞的基因表达分析。
结果
白花丹醌处理诱导人乳腺癌细胞发生细胞毒性，同时导致细胞周期停滞、DNA 损伤和细胞死亡，从而引发细胞凋亡。还发现白花丹醌抑制癌细胞中端粒酶的活性，导致端粒损耗。端粒缩短通过染色体末端的端粒荧光减少和基因组不稳定性得到证实。
结论
这些发现表明，白花丹醌可能作为乳腺癌治疗的辅助手段。
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