碘和δ-碘代戊内酯在甲状腺上皮癌细胞和乳腺癌细胞生长和凋亡中的作用。

The role of iodine and delta-iodolactone in growth and apoptosis of malignant thyroid epithelial cells and breast cancer cells.

机构信息

Department of Endocrinology, University of Munich, Germany.

出版信息

Hormones (Athens). 2010 Jan-Mar;9(1):60-6. doi: 10.14310/horm.2002.1254.

DOI:10.14310/horm.2002.1254

PMID:20363723

Abstract

OBJECTIVE

As we previously demonstrated, the inhibitory effect of iodine on thyroid cell growth is mediated by iodolactones, especially 6-iodo-5-hydroxy-eicosatrienoic acid (delta-iodolactone). In this communication we compare the effect of iodide, molecular iodine and delta-iodolactone on growth inhibition and apoptosis on three human thyroid carcinoma cell lines (B-CPAP cells, FTC-133 cells and 8505C cells) as well as on human breast cancer cells (MCF 7).

METHODS

Thyroid carcinoma cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and MCF 7 cells in Rowswell Park Memorial Institute (RPMI) culture medium, both containing 10% (v/v) Fetal Calf Serum (FCS), until they were confluent. Around 2000 cells were then distributed in 12-well plates and grown for 48 h in either DMEM (thyroid cancer cells) or in RPMI medium (MCF 7 cells) both containing 5% FCS. Thereafter, different concentrations of iodide, iodine or delta-iodolactone were added for 24 h. Growth rate was estimated by cell counting in a Coulter Counter adapted for epithelial cells. Apoptosis was determined by a mitochondrial potential assay.

RESULTS

The growth rate of B-CPAP cells was unaffected by iodide, but was reduced by high concentreations of molecular iodine (100 and 500 microM). However, delta-iodolactone significantly reduced cell proliferation already with low concentrations (5 microM and 10 microM) and further in a dose-dependent manner up to 82%. FTC-133 and 8505C cells were unaffected by iodide, iodine or delta-iodolactone. In contrast, in MCF 7 cells, molecular iodine (100 microM) inhibited growth from 100% to 83% but delta-iodolactone (1, 5 and 10 microM) dose-dependently decreased growth rate from 100% to 82% and 62%, respectively. The inhibition of growth was through apoptosis, and not necrosis, as the amount of apoptotic cells corresponded to the growth inhibition.

CONCLUSION

delta-Iotaodolactone seems to be the main iodocompound which can inhibit growth and induce apoptosis in B-CPAP cells as well as in MCF 7 breast cancer cells.

摘要

目的

正如我们之前所证明的，碘对甲状腺细胞生长的抑制作用是通过碘内酯介导的，特别是 6-碘-5-羟基二十碳三烯酸（δ-碘内酯）。在本通讯中，我们比较了碘化物、分子碘和 δ-碘内酯对三种人甲状腺癌细胞系（B-CPAP 细胞、FTC-133 细胞和 8505C 细胞）以及人乳腺癌细胞（MCF7）生长抑制和凋亡的影响。

方法

甲状腺癌细胞在杜尔贝科改良伊格尔培养基（DMEM）中培养，MCF7 细胞在罗威尔帕克纪念研究所（RPMI）培养基中培养，均含 10%（v/v）胎牛血清（FCS），直至细胞融合。然后将大约 2000 个细胞分布在 12 孔板中，在含有 5%FCS 的 DMEM（甲状腺癌细胞）或 RPMI 培养基（MCF7 细胞）中生长 48 小时。然后，加入不同浓度的碘化物、碘或 δ-碘内酯 24 小时。通过适用于上皮细胞的库尔特计数器计数来估计生长速度。通过线粒体电位测定法确定细胞凋亡。

结果

B-CPAP 细胞的生长速度不受碘化物影响，但高浓度的分子碘（100 和 500μM）可降低其生长速度。然而，δ-碘内酯已用低浓度（5μM 和 10μM）显著降低细胞增殖，并进一步呈剂量依赖性方式降低至 82%。FTC-133 和 8505C 细胞不受碘化物、碘或 δ-碘内酯影响。相比之下，在 MCF7 细胞中，分子碘（100μM）将生长抑制从 100%降低至 83%，但 δ-碘内酯（1、5 和 10μM）则剂量依赖性地将生长速度从 100%降低至 82%和 62%。生长抑制是通过细胞凋亡而不是坏死实现的，因为凋亡细胞的数量与生长抑制相对应。