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Iron(II)−Polypyridyl Complexes Inhibit the Growth of Glioblastoma Tumor and Enhance TRAIL‐Induced Cell Apoptosis
Author(s) -
Lin Hao,
Wang Yifan,
Lai Haoqiang,
Li Xiaoling,
Chen Tianfeng
Publication year - 2018
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201800862
Subject(s) - apoptosis , cancer cell , cancer research , tumor necrosis factor alpha , cancer , cell growth , programmed cell death , chemistry , cell culture , biology , medicine , immunology , biochemistry , genetics
A promising cancer‐targeting agent for the induction of apoptosis in tumor necrosis factor (TNF) proteins, the TNF‐related apoptosis‐inducing ligand (TRAIL) ligand, has found limited applications in the treatment of cancer cells, owing to its resistance by cancer cell lines. Therefore, the rational design of anticancer agents that could sensitize cancer cells towards TRAIL is of great significance. Herein, we report that synthetic iron(II)−polypyridyl complexes are capable of inhibiting the proliferation of glioblastoma cancer cells and efficiently enhancing TRAIL‐induced cell apoptosis. Mechanistic studies demonstrated that the synthesized complexes induced cancer‐cell apoptosis through triggering the activation of p38 and p53 and inhibiting the activation of ERK. Moreover, uPA and MMP‐2/MMP‐9, among the most important metastatic regulatory proteins, were also found to be significantly alerted after the treatment. Furthermore, we also found that tumor growth in nude mice was significantly inhibited by iron complex Fe2 through the induction of apoptosis without clear systematic toxicity, as indicated by histological analysis. Taken together, this study provides evidence for the further development of metal‐based anticancer agents and chemosensitizers of TRAIL for the treatment of human glioblastoma cancer cells.