Holy Jon M
Department of Anatomy and Cell Biology, UMD School of Medicine, 10 University Drive, Duluth, MN 55812-2487, USA.
Mutat Res. 2002 Jun 27;518(1):71-84. doi: 10.1016/s1383-5718(02)00076-1.
The dietary phytochemical curcumin possesses anti-inflammatory, -oxidant, and cytostatic properties, and exhibits significant potential as a chemopreventative agent in humans. Although many cell types are arrested in the G2/M-phase of the cell cycle after curcumin treatment, the mechanisms by which this occurs are not well understood. The purpose of this study was to examine the effects of curcumin on the cell cycle of MCF-7 breast cancer cells to determine whether growth arrest is associated with structural changes in cellular organization during mitosis. For this purpose, MCF-7 breast cancer cells were treated with 10-20 microM curcumin, and the effects on cell proliferation and mitosis studied. Structural changes were monitored by immunolabeling cells with antibodies to a number of cytoplasmic and nuclear proteins, including beta-tubulin, NuMA, lamins A/C and B1, lamin B receptor, and centromere antigens. At the concentrations used, a single dose of curcumin does not induce significant apoptosis, but is highly effective in inhibiting cell proliferation for over 6 days. During the first 24-48 h of treatment, many cells are arrested in M-phase, and DNA synthesis is almost completely inhibited. Remarkably, arrested mitotic cells exhibit monopolar spindles, and chromosomes do not undergo normal anaphase movements. After 48 h, most cells eventually leave M-phase, and many form multiple micronuclei instead of individual daughter nuclei. These observations indicate that the curcumin-induced G2/M arrest previously described for MCF-7 cells is due to the assembly of aberrant, monopolar mitotic spindles that are impaired in their ability to segregate chromosomes. The production of cells with extensive micronucleation after curcumin treatment suggests that at least some of the cytostatic effects of this phytochemical are due to its ability to disrupt normal mitosis, and raises the possibility that curcumin may promote genetic instability under some circumstances.
膳食植物化学物姜黄素具有抗炎、抗氧化和抑制细胞生长的特性，在人类中作为化学预防剂显示出巨大潜力。尽管许多细胞类型在姜黄素处理后会停滞在细胞周期的G2/M期，但其发生机制尚不清楚。本研究的目的是研究姜黄素对MCF-7乳腺癌细胞周期的影响，以确定生长停滞是否与有丝分裂期间细胞组织结构的变化有关。为此，用10-20微摩尔姜黄素处理MCF-7乳腺癌细胞，并研究其对细胞增殖和有丝分裂的影响。通过用针对多种细胞质和核蛋白的抗体对细胞进行免疫标记来监测结构变化，这些蛋白包括β-微管蛋白、核有丝分裂器蛋白、核纤层蛋白A/C和B1、核纤层蛋白B受体以及着丝粒抗原。在所使用的浓度下，单剂量姜黄素不会诱导明显的细胞凋亡，但在抑制细胞增殖超过6天方面非常有效。在处理的最初24-48小时内，许多细胞停滞在M期，DNA合成几乎完全受到抑制。值得注意的是，停滞的有丝分裂细胞呈现单极纺锤体，染色体不进行正常的后期运动。48小时后，大多数细胞最终离开M期，许多细胞形成多个微核而不是单个子核。这些观察结果表明，先前描述的MCF-7细胞中姜黄素诱导的G2/M停滞是由于异常单极有丝分裂纺锤体的组装，其分离染色体的能力受损。姜黄素处理后产生大量微核的细胞表明，这种植物化学物的至少一些抑制细胞生长的作用是由于其破坏正常有丝分裂的能力，并增加了姜黄素在某些情况下可能促进遗传不稳定的可能性。
