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肉桂醛单独及与阿霉素联合对U87MG细胞的细胞毒性和诱导凋亡作用的评估。

Evaluation of the cytotoxic and apoptogenic effects of cinnamaldehyde on U87MG cells alone and in combination with doxorubicin.

作者信息

Abbasi Abbas, Hajialyani Marziyeh, Hosseinzadeh Leila, Jalilian Fereshteh, Yaghmaei Parichehr, Jamshidi Navid Sahar, Motamed Hajar

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, I.R. Iran.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

出版信息

Res Pharm Sci. 2020 Feb 20;15(1):26-35. doi: 10.4103/1735-5362.278712. eCollection 2020 Feb.

Abstract

BACKGROUND AND PURPOSE

In the present study, we tried for the first time to examine whether cinnamaldehyde (CA), with herbal nature, can be co-administrated with doxorubicin (DOX, as an anticancer drug) toward U87MG glioblastoma cells to potentiate its cytotoxic effect and overcome or reduce its side effects.

EXPERIMENTAL APPROACH

The cytotoxic effect of DOX and CA, either individually or in combination, were evaluated on U87MG cells using the MTT method. The mechanism of action was studied by investigating the mode of cell death using caspase-3 and 9 activations, mitochondrial membrane potential (MMP) as well as sub G1 analysis. The expression of apoptosis- related genes (Bcl-2 and Bax) was also examined.

FINDINGS / RESULTS: Cellular toxicity assay revealed that CA and DOX can potentially reduce the viability of U87MG cells with IC50 at 11.6 and 5 μg/mL, respectively. Exposure with the combination of CA and DOX significantly increased cytotoxic effect of DOX on U87MG cells. The results of SUBG1, MMP, and also caspase-3 and -9 activity assays, in association with the results corresponding to the Bax and Bcl-2 gene expressions, altogether revealed that CA can induce apoptosis on U87MG cells. Moreover, apoptogenic effects of DOX were found to be potentiated by CA.

CONCLUSION AND IMPLICATIONS

The results of this study revealed the promising cytotoxic and apoptogenic role of CA on U87MG cells. Additionally, our findings demonstrated that CA is able to enhance the apoptosis induced by DOX on human glioblastoma cells. Collectively, these data suggested that co-exposure of CA and DOX could be effective for treatment of glioblastoma, but further and clinical studies are still needed to prove these results.

摘要

背景与目的

在本研究中,我们首次尝试探究具有草药性质的肉桂醛(CA)是否可与阿霉素(DOX,一种抗癌药物)联合用于U87MG胶质母细胞瘤细胞,以增强其细胞毒性作用并克服或减轻其副作用。

实验方法

采用MTT法评估DOX和CA单独或联合使用对U87MG细胞的细胞毒性作用。通过研究半胱天冬酶-3和-9的激活、线粒体膜电位(MMP)以及亚G1期分析来研究细胞死亡模式,从而探究其作用机制。还检测了凋亡相关基因(Bcl-2和Bax)的表达。

研究结果

细胞毒性试验表明,CA和DOX均可降低U87MG细胞的活力,其IC50分别为11.6和5μg/mL。CA与DOX联合使用显著增强了DOX对U87MG细胞的细胞毒性作用。亚G1期、MMP以及半胱天冬酶-3和-9活性测定的结果,与Bax和Bcl-2基因表达的相应结果一起,共同表明CA可诱导U87MG细胞凋亡。此外,发现CA可增强DOX的凋亡诱导作用。

结论与意义

本研究结果揭示了CA对U87MG细胞具有良好的细胞毒性和凋亡诱导作用。此外,我们的研究结果表明,CA能够增强DOX对人胶质母细胞瘤细胞的凋亡诱导作用。总体而言,这些数据表明CA与DOX联合使用可能对胶质母细胞瘤的治疗有效,但仍需要进一步的临床研究来证实这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39c2/7053293/e02d107f8536/RPS-15-26-g001.jpg

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