A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells.

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Shen H, Zhu H, Song M, Tian Y, Huang Y, Zheng H, Cao R, Lin J, Bi Z, Zhong W

A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells.

BMC Cancer. 2014 Aug 29;14:629. doi: 10.1186/1471-2407-14-629.

PubMed ID
25167922 [ View in PubMed
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Abstract

BACKGROUND: The 90-kDa heat shock protein HSP90AA1 is critical for the stability of several proteins that are important for tumor progression and thus, is a promising target for cancer therapy. Selenosemicarbazone metal complexes have been shown to possess anticancer activity through an unknown molecular mechanism. METHODS: The MTT assay, fluorescence-activated cell sorting, and fluorescent microscopy were used to analyze the mechanism of the anti-cancer activity of the selenosemicarbazone metal complexes. Additionally, RNA-seq was applied to identify transcriptional gene changes, and in turn, the signaling pathways involved in the process of 2-24a/Cu-induced cell death. Last, the expression of HSP90AA1, HSPA1A, PIM1, and AKT proteins in 2-24a/Cu-treated cells were investigated by western blot analysis. RESULTS: A novel selenosemicarbazone copper complex (2-24a/Cu) efficiently induced G2/M arrest and was cytotoxic in cancer cells. 2-24a/Cu significantly induced oxidative stress in cancer cells. Interestingly, although RNA-seq revealed that the transcription of HSP90AA1 was increased in 2-24a/Cu-treated cells, western blotting showed that the expression of HSP90AA1 protein was significantly decreased in these cells. Furthermore, down-regulation of HSP90AA1 led to the degradation of its client proteins (PIM1 and AKT1), which are also cancer therapy targets. CONCLUSION: Our results showed that 2-24a/Cu efficiently generates oxidative stress and down-regulates HSP90AA1 and its client proteins (PIM1, AKT1) in U2os and HeLa cells. These results demonstrate the potential application of this novel copper complex in cancer therapy.