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Exploring cysteine regulation in cancer cell survival with a highly specific “Lock and Key” fluorescent probe for cysteine

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Abstract

To probe the regulatory roles of cysteine (Cys) in cancer cell survival, a highly selective and sensitive fluorescent Cys probe SiR was developed by employing a novel “lock and key” strategy, which allows Cys to be detected without any interference or probe consumption caused by the intracellular high concentration of glutathione (GSH). Using SiR, we confirmed that inhibiting cystine (Cys2) transporter system xc to deplete intracellular Cys is more efficient than inhibiting glutamate–cysteine ligase GCL to deplete intracellular GSH for sensitizing cancer cells to chemotherapy. Moreover, with the probe, a possible self-protection mechanism of cancer cells was indicated: when extracellular Cys sources are blocked, cancer cells could still survive by multidrug resistance protein transporter (Mrp1)-mediated export of intracellular GSH/GSSG as sources to supply intracellular Cys for resisting detrimental oxidative stress. Based on this finding, we further confirmed that abrogating the self-protection mechanism is an even more efficient strategy for sensitizing cancer cells to chemotherapy.

Graphical abstract: Exploring cysteine regulation in cancer cell survival with a highly specific “Lock and Key” fluorescent probe for cysteine

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Publication details

The article was received on 30 May 2019, accepted on 03 Sep 2019 and first published on 07 Sep 2019


Article type: Edge Article
DOI: 10.1039/C9SC02618E
Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY license
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    Exploring cysteine regulation in cancer cell survival with a highly specific “Lock and Key” fluorescent probe for cysteine

    J. Liu, M. Liu, H. Zhang, X. Wei, J. Wang, M. Xian and W. Guo, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C9SC02618E

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