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Nutrients. 2019 Aug 16;11(8). pii: E1926. doi: 10.3390/nu11081926.

Targeting Glutathione Metabolism: Partner in Crime in Anticancer Therapy.

Author information

1
Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, 00133 Rome, Italy.
2
IRCCS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy.
3
Department of Biology, University of Rome "Tor Vergata", Via della Ricerca Scientifica, 00133 Rome, Italy. ciriolo@bio.uniroma2.it.
4
IRCCS San Raffaele Pisana, Via della Pisana 235, 00163 Rome, Italy. ciriolo@bio.uniroma2.it.

Abstract

Glutathione (GSH) is the predominant low-molecular-weight antioxidant with a ubiquitous distribution inside the cell. The steady-state level of cellular GSH is dependent on the balance between synthesis, hydrolysis, recycling of glutathione disulphide (GSSG) as well as cellular extrusion of reduced, oxidized, or conjugated-forms. The augmented oxidative stress typical of cancer cells is accompanied by an increase of glutathione levels that confers them growth advantage and resistance to a number of chemotherapeutic agents. Targeting glutathione metabolism has been widely investigated for cancer treatment although GSH depletion as single therapeutic strategy has resulted largely ineffective if compared with combinatorial approaches. In this review, we circumstantiate the role of glutathione in tumour development and progression focusing on how interfering with different steps of glutathione metabolism can be exploited for therapeutic purposes. A dedicated section on synthetic lethal interactions with GSH modulators will highlight the promising option of harnessing glutathione metabolism for patient-directed therapy in cancer.

KEYWORDS:

GSH; cancer therapy; ferroptosis; synthetic lethality

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