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姜黄素对正常和癌变哺乳动物上皮细胞的纳米力学的差异影响。

Differential effect of curcumin on the nanomechanics of normal and cancerous Mammalian epithelial cells.

机构信息

Laboratoire Charles Coulomb UMR 5221, Université Montpellier 2, 34095, Montpellier, France.

出版信息

Cell Biochem Biophys. 2013 Apr;65(3):399-411. doi: 10.1007/s12013-012-9443-1.

DOI:10.1007/s12013-012-9443-1
PMID:23097022
Abstract

Though the pharmacological activity of curcumin inhibiting the proliferation of certain cancer cells in culture was demonstrated, its effect on early-stage modifications induced in cell mechanics influencing hereby cell growth and cell adhesion are still questionable. We investigate the morphology and the elastic properties of live cultured, non-malignant human mammalian epithelial cells (HMEC) and cancerous breast epithelial cells (MCF7) by atomic force microscopy. We describe the different behavior of the two similar cell lines under curcumin treatment and we use fluorescence microscopy to identify the microtubules as the cytoskeleton structures responding to curcumin. The first changes in the HMEC cell morphology are observed after already 2 h incubation with curcumin. A 6-h long treatment leaves the MCF7 cells morphology non-affected, but the microtubules of HMEC cells disassemble and form a ring-like organization circumscribing the nuclear area. The observed morphological changes were correlated to modifications in cell's mechanics via elasticity force mapping measurements. Curcumin treatment modified elasticity of the HMEC cells increasing the cell's average Young's modulus two- to threefold, especially in the cytoplasmic area. Contrariwise, a slight decrease in the Young's modulus was noticed for the MCF7 cells, as they become softer due to the action of curcumin. Chemotherapeutic drugs exert their effect via the perturbation of the dynamic instability of the microtubule, hence the cell-specific perturbation induced by curcumin can help in future understanding of drug induced events on the cell behavior.

摘要

尽管姜黄素抑制某些癌细胞在培养中增殖的药理学活性已得到证明,但它对细胞力学引起的早期变化的影响,从而影响细胞生长和细胞黏附,仍然存在疑问。我们通过原子力显微镜研究了活培养的非恶性人类哺乳动物上皮细胞(HMEC)和癌性乳腺上皮细胞(MCF7)的形态和弹性特性。我们描述了两种相似的细胞系在姜黄素处理下的不同行为,并使用荧光显微镜鉴定微管作为对姜黄素做出响应的细胞骨架结构。HMEC 细胞在姜黄素孵育 2 小时后,其形态就发生了最初的变化。6 小时的处理不会影响 MCF7 细胞的形态,但 HMEC 细胞的微管会解体,并形成一个环状结构环绕核区。观察到的形态变化与通过弹性力映射测量细胞力学的变化相关联。姜黄素处理改变了 HMEC 细胞的弹性,使细胞的平均杨氏模量增加了两到三倍,特别是在细胞质区域。相反,MCF7 细胞的杨氏模量略有下降,因为它们因姜黄素的作用而变得更软。化疗药物通过微管的动态不稳定性的干扰发挥作用,因此,姜黄素诱导的细胞特异性干扰有助于未来理解药物对细胞行为的诱导事件。

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引用本文的文献

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The roles of cellular nanomechanics in cancer.细胞纳米力学在癌症中的作用。
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Cancer Res. 2014 Feb 15;74(4):1250-60. doi: 10.1158/0008-5472.CAN-13-1778. Epub 2013 Dec 26.