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胸腺醌诱导人肺腺癌细胞的抗肿瘤和凋亡。

Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells.

机构信息

Department of Basic Medical Science, Neyshabur University of Medical Sciences, Neyshabur, Iran.

Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

J Cell Physiol. 2019 Jul;234(7):10421-10431. doi: 10.1002/jcp.27710. Epub 2018 Nov 1.

DOI:10.1002/jcp.27710
PMID:30387147
Abstract

BACKGROUND

Lung cancer has been associated with the highest cancer-associated mortality rate in the world. Chemotherapeutic management of cancer necessitates introducing new promising agents. Plants represent a rich source of new antineoplastic and chemotherapeutic agents. Thymoquinone (TQ), the main constituent of Nigella sativa (black seed or black cumin), has shown potent antioxidant and anti-inflammatory activities so far. The purpose of the current study was to evaluate the antineoplastic potential of TQ and their underlying mechanisms in A549 cells (human lung cancer cell line).

METHOD

The A549 cells were treated with the different concentrations of TQ for three following days. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Necrosis and apoptosis were assessed by fluorescence-activated cell sorter analysis through propidium iodide and annexin V staining and also by assessing caspase-3 and -9 activation. DNA fragmentation was monitored by gel electrophoresis.

RESULTS

TQ decreased the viability and increased apoptotic cell death in A549 human lung tumor cells. TQ treatment significantly elevated the Bax/ Bcl-2 ratio in the lung cancer cells. TQ also upregulated p53 expression, another apoptotic modulator in A549 cancer cells. TQ also activated caspase-dependent apoptosis by the activation of caspases-3 and -9.

CONCLUSION

Our results proposed that TQ may be a potential new therapeutic agent for the management of lung cancer. TQ promoted apoptosis in A546 lung cancer cells by the activation of p53 and caspase cascade dependent pathways.

摘要

背景

肺癌是全球癌症相关死亡率最高的癌症。癌症的化学治疗管理需要引入新的有前途的药物。植物是新的抗肿瘤和化疗药物的丰富来源。迄今为止,姜黄素(TQ),黑种草(黑种子或黑孜然)的主要成分,已显示出强大的抗氧化和抗炎活性。本研究的目的是评估 TQ 在 A549 细胞(人肺癌细胞系)中的抗肿瘤潜力及其潜在机制。

方法

用不同浓度的 TQ 处理 A549 细胞 3 天。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)测定法评估细胞活力。通过碘化丙啶(PI)和膜联蛋白 V 染色的荧光激活细胞分选(FACS)分析以及评估半胱天冬酶-3 和 -9 的激活来评估坏死和细胞凋亡。通过凝胶电泳监测 DNA 片段化。

结果

TQ 降低了 A549 人肺癌肿瘤细胞的活力并增加了细胞凋亡。TQ 处理显著增加了肺癌细胞中的 Bax/Bcl-2 比值。TQ 还上调了 p53 表达,这是 A549 癌细胞中的另一种凋亡调节剂。TQ 通过激活 caspase-3 和 -9 还激活了 caspase 依赖性凋亡。

结论

我们的结果表明 TQ 可能是治疗肺癌的潜在新治疗剂。TQ 通过激活 p53 和 caspase 级联依赖性途径促进 A546 肺癌细胞凋亡。

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