菊花素使人肺癌细胞对肿瘤坏死因子相关凋亡诱导配体(TRAIL)介导的凋亡敏感

S. Mehdi, Zafaryab, S. Nafees, Asad Mahmood Khan, I. Ahmad, Z. Hafeez, M. M. Rizvi
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引用次数: 10

摘要

背景:肺癌是世界范围内癌症死亡的主要原因。因此,需要更连贯的方法来治疗肺癌。目的:菊花素(5,7 -二羟基黄酮)是一种天然存在的类黄酮,具有广泛的药理特性,通常存在于水果、蔬菜、蜂蜜和蜂胶中。在我们的研究中,我们假设菊花素对L132肺癌细胞系具有抗癌活性。方法:采用MTT法和NRU法测定其细胞毒作用。DAPI法评价细胞死亡情况。Western Blot法检测促凋亡蛋白和抗凋亡蛋白的表达,RT-PCR法检测mRNA的表达。用硅片研究了菊花素,以确定合适的抑制蛋白功能的抑制剂。结果:结果表明,与肿瘤坏死因子TNF-α相比,金菊花素对L132肺癌细胞存活的抑制作用增强,48小时后DAPI(4′,6-二氨基-2-苯基吲哚)染色观察到细胞核形态的改变。黄菊花素通过增加凋亡相关蛋白caspase-3、8、9和Bax的表达来增强trail诱导的细胞凋亡,而Bcl-2的表达则降低。Chrysin与caspase-3、8、9、Bax和Bcl-2蛋白对接,以确定合适的抑制蛋白功能的抑制剂。结论:我们得出的结论是,菊花素对trail诱导的肺癌细胞凋亡敏感,可能被认为是未来研究中有希望的治疗人类肺癌的候选药物。
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Chrysin Sensitizes Human Lung Cancer Cells to Tumour Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) Mediated Apoptosis
Background: Lung cancer is the primary cause of cancer deaths worldwide. Thus, the requisite for more coherent methods to lung cancer therapy is needed. Purpose: Chrysin (5, 7-dihydroxyflavone) is a naturally occurring flavonoid having a wide range of pharmacological properties and is commonly found in fruits, vegetables, honey and propolis. In our study, we have hypothesized that chrysin would have anticancer activity on L132 lung cancer cell line.Methods: The cytotoxic effects were assessed by MTT and NRU assay. DAPI was used to evaluate the cell death. The pro- or anti-apoptotic proteins were detected by Western Blot assay, and, besides, mRNA expression was analysed with RT-PCR. In silico study of chrysin was performed to identify suitable inhibitors against the protein function. Results: Results indicated that chrysin enhanced the inhibitory effects of TRAIL (Tumour Necrosis Factor Related Apoptosis-Inducing Ligand) in comparison to TNF-α (tumour necrosis factor) on cell viability in L132 lung cancer cells and altered nuclear morphology of cells was observed in DAPI (4’,6-diamidino-2-phenylindole) staining after 48 hrs treatment. Treatment with chrysin enhances TRAIL-induced apoptosis by increasing the expression of apoptosis-related proteins including caspase-3, 8, 9 and Bax, whereas the expression of Bcl-2 was decreased. Chrysin was docked with caspase-3, 8, 9, Bax, and Bcl-2 proteins to identify suitable inhibitors against the protein function.Conclusion: We concluded that chrysin sensitizes lung cancer cells to TRAIL-induced apoptosis and may be considered for future studies as a promising therapeutic candidate for human lung cancer.
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