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Article

Gallic Acid Triggers Iron-Dependent Cell Death with Apoptotic, Ferroptotic, and Necroptotic Features

School of Life Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
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Author to whom correspondence should be addressed.
Received: 28 July 2019 / Revised: 18 August 2019 / Accepted: 21 August 2019 / Published: 26 August 2019
(This article belongs to the Special Issue Basic Research for the Potential Use of Plant Toxins)
Gallic acid (GA) is a natural anti-cancer compound that can be found in many food sources, including edible mushrooms, fruits, and vegetables. Studies generally attribute the anti-cancer activity of GA to the induction of apoptosis. Here, we reported that GA activated iron-dependent cell death mechanisms with apoptotic, ferroptotic, and necroptotic features. Our time-lapse live-cell microscopy study demonstrated that GA could induce coexistence of multiple types of cell death pathways, including apoptosis characterized by mitochondrial cytochrome c release and caspase-3 activation, ferroptosis characterized by lipid peroxidation, and necroptosis characterized by the loss of plasma membrane integrity. This GA-induced cell death could be completely suppressed by exposure to an iron chelator deferoxamine, indicating that it is an iron-dependent cell death process. Importantly, MLKL (mixed lineage kinase domain-like protein) inhibitor necrosulfonamide exerted a synergistic effect by increasing the sensitivity of cancer cells to GA. Taken together, our results provide new mechanistic insights, and also suggest new strategies to enhance the efficacy of this natural anti-cancer compound by identifying the agents that can promote or suppress the GA-induced cell death process. View Full-Text
Keywords: apoptosis; cell death; deferoxamine; ferroptosis; gallic acid; necroptosis; necrosulfonamide apoptosis; cell death; deferoxamine; ferroptosis; gallic acid; necroptosis; necrosulfonamide
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MDPI and ACS Style

Tang, H.M.; Cheung, P.C.K. Gallic Acid Triggers Iron-Dependent Cell Death with Apoptotic, Ferroptotic, and Necroptotic Features. Toxins 2019, 11, 492. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11090492

AMA Style

Tang HM, Cheung PCK. Gallic Acid Triggers Iron-Dependent Cell Death with Apoptotic, Ferroptotic, and Necroptotic Features. Toxins. 2019; 11(9):492. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11090492

Chicago/Turabian Style

Tang, Ho M., and Peter C.K. Cheung 2019. "Gallic Acid Triggers Iron-Dependent Cell Death with Apoptotic, Ferroptotic, and Necroptotic Features" Toxins 11, no. 9: 492. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins11090492

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