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渥曼青霉素通过凋亡途径诱导 MCF-7 乳腺癌细胞死亡,涉及染色质浓缩、活性氧的产生和细胞膜起泡。

Wortmannin induces MCF-7 breast cancer cell death via the apoptotic pathway, involving chromatin condensation, generation of reactive oxygen species, and membrane blebbing.

机构信息

Applied Biosciences Emphasis, Department of Applied Science, University Arkansas at Little Rock, Little Rock, AR, USA.

Graduate Institute of Technology, University Arkansas at Little Rock, Little Rock, AR, USA.

出版信息

Breast Cancer (Dove Med Press). 2012 Jul 13;4:103-13. doi: 10.2147/BCTT.S31712. eCollection 2012.

Abstract

BACKGROUND

Apoptosis can be used as a reliable marker for evaluating potential chemotherapeutic agents. Because wortmannin is a microbial steroidal metabolite, it specifically inhibits the phosphatidyl inositol 3-kinase pathway, and could be used as a promising apoptosis-based therapeutic agent in the treatment of cancer. The objective of this study was to investigate the biomolecular mechanisms involved in wortmannin-induced cell death of breast cancer-derived MCF-7 cells.

METHODS AND RESULTS

Our experimental results demonstrate that wortmannin has strong apoptotic effects through a combination of different actions, including reduction of cell viability in a dose-dependent manner, inhibition of proliferation, and enhanced generation of intracellular reactive oxygen species.

CONCLUSION

Our findings suggest that wortmannin induces MCF-7 cell death via a programmed pathway showing chromatin condensation, nuclear fragmentation, reactive oxygen species, and membrane blebbing, which are characteristics typical of apoptosis.

摘要

背景

细胞凋亡可作为评估潜在化疗药物的可靠标志物。由于渥曼青霉素是一种微生物甾体代谢物,它特异性地抑制磷脂酰肌醇 3-激酶途径,因此可作为一种有前途的基于凋亡的抗癌治疗剂。本研究的目的是探讨渥曼青霉素诱导乳腺癌衍生的 MCF-7 细胞死亡的生物分子机制。

方法与结果

我们的实验结果表明,渥曼青霉素通过多种作用的结合具有很强的凋亡作用,包括剂量依赖性地降低细胞活力、抑制增殖和增强细胞内活性氧的产生。

结论

我们的研究结果表明,渥曼青霉素通过一种程序性途径诱导 MCF-7 细胞死亡,表现为染色质浓缩、核碎裂、活性氧和细胞膜起泡,这些都是凋亡的典型特征。

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