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铁去除增强维生素 C 诱导的 K-562 白血病细胞凋亡和生长抑制。

Iron removal enhances vitamin C-induced apoptosis and growth inhibition of K-562 leukemic cells.

机构信息

Research Center for Cancer Stem Cell, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.

Division of Hematology/Oncology, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.

出版信息

Sci Rep. 2018 Nov 26;8(1):17377. doi: 10.1038/s41598-018-35730-8.

Abstract

Although vitamin C (VC) has recently garnered interest as an alternative cancer therapy, its clinical effects remain controversial. It was recently reported using in vitro prostate cancer cell lines that excess extracellular iron (EEI) diminishes anti-cancer effects of VC, promoting the decomposition of hydrogen peroxide (HO) generated by VC. Here we demonstrated that EEI diminished the inhibitory effect of VC on the survival of K562 human leukemic cells in vitro, by reducing the amount of HO and abrogating the apoptosis pathways induced by VC. In vivo, in the presence of EEI, the growth inhibitory effect of VC on K562 cells was completely abrogated; in fact, VC enhanced K562 cell growth. Reduction of EEI restored the apoptosis-inducing effect of VC in vitro and enhanced the growth inhibitory effect of VC in vivo. Further studies are warranted to investigate whether the combination of VC and iron depletion has similar effects in various other leukemic or cancer cells against which VC has been effective in previous experimental studies.

摘要

尽管维生素 C(VC)最近作为一种癌症治疗的替代方法引起了关注,但它的临床效果仍存在争议。最近有研究报告称,在体外前列腺癌细胞系中,过量的细胞外铁(EEI)会降低 VC 的抗癌作用,促进 VC 产生的过氧化氢(HO)的分解。在这里,我们证明 EEI 通过减少 HO 的量并阻断 VC 诱导的细胞凋亡途径,从而降低 VC 对体外 K562 人白血病细胞存活的抑制作用。在体内,当存在 EEI 时,VC 对 K562 细胞的生长抑制作用完全被阻断;事实上,VC 增强了 K562 细胞的生长。降低 EEI 恢复了 VC 在体外诱导细胞凋亡的作用,并增强了 VC 在体内的生长抑制作用。需要进一步的研究来探讨 VC 和铁耗竭的联合应用是否对其他白血病或癌症细胞具有类似的效果,因为 VC 在以前的实验研究中对这些细胞有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dafa/6255900/1edcdf776769/41598_2018_35730_Fig1_HTML.jpg

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