Pramchu-em Chalamart, Meksawan Kulwara, Chanvorachote Pithi
a Department of Food and Pharmaceutical Chemistry and Cell-Based Drug and Health Product Development Research Unit , Chulalongkorn University , Bangkok Thailand.
b Department of Pharmacol?ogy and Physiology , Faculty of Pharmaceutical Sciences and Cell-Based Drug and Health Product Development Research Unit, Chulalongkorn University , Bangkok , Thailand.
Nutr Cancer. 2016;68(2):312-9. doi: 10.1080/01635581.2016.1142582. Epub 2016 Feb 29.
Anoikis is a particular type of apoptosis induced by the loss of cell attachment from extracellular matrix. It has been shown to play a critical role in the inhibition of cancer metastasis. Herein, we report for the first time that zinc, an essential trace element, has anoikis sensitizing activity against lung cancer cells. An anoikis assay showed that zinc treatment at the concentrations of 0-50 µM enhanced the anoikis response in human lung cancer H460 cells with significant decreased cell viability and increased number of apoptosis cells detected with Hoechst 33342 and PI co-staining assay. Moreover, zinc significantly inhibited the growth of cancer cells in an anchorage-independent condition. This is mediated through the zinc-induced decrease in prosurvival active protein kinase B (Akt) and metastasis-regulating caveolin-1 (Cav-1) protein expression. Taken together, our results indicate that zinc sensitizes non-small cell lung cancer cells to anoikis and may play a role in the prevention of cancer metastasis.
失巢凋亡是一种由细胞与细胞外基质失去附着而诱导的特殊类型的细胞凋亡。研究表明，它在抑制癌症转移中起着关键作用。在此，我们首次报道锌这种必需微量元素对肺癌细胞具有失巢凋亡敏化活性。失巢凋亡试验表明，0 - 50 µM浓度的锌处理增强了人肺癌H460细胞的失巢凋亡反应，细胞活力显著降低，通过Hoechst 33342和PI共染色检测到的凋亡细胞数量增加。此外，锌在非锚定依赖条件下显著抑制癌细胞生长。这是通过锌诱导的促生存活性蛋白激酶B（Akt）和转移调节蛋白小窝蛋白-1（Cav-1）蛋白表达降低介导的。综上所述，我们的结果表明锌使非小细胞肺癌细胞对失巢凋亡敏感，并可能在预防癌症转移中发挥作用。
