Cell death induced by 2-phenylethynesulfonamide uncovers a pro-survival function of BAX

Mattiolo, Paolo; Barbero-Farran A.; Amigó J.; Ripamonti M.; Ribas i Fortuny, Judit; Boix Torras, Jacint

doi:https://doi.org/10.1016/j.canlet.2014.07.037

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Issue date

2014

Author

Mattiolo, Paolo

Barbero-Farran A.

Amigó J.

Ripamonti M.

Ribas i Fortuny, Judit

Boix Torras, Jacint

Suggested citation

Mattiolo, Paolo; Barbero-Farran A.; Amigó J.; Ripamonti M.; Ribas i Fortuny, Judit; Boix Torras, Jacint; . (2014) . Cell death induced by 2-phenylethynesulfonamide uncovers a pro-survival function of BAX. Cancer Letters, 2014, vol. 354, num. 1, p. 115-121. https://doi.org/10.1016/j.canlet.2014.07.037.

Abstract

PES (2-phenylethynesulfonamide) was initially identified as an inhibitor of p53 translocation to mitochondria and named Pifithrin-µ. Further studies showed that PES selectively killed tumour cells and was thus a promising anticancer agent. PES-induced cell death was characterised by a non-apoptotic,

autophagosome-rich phenotype. We observed this phenotype via electron microscopy in wild type (wt) and double Bax-/- Bak-/- (DKO) mouse embryonic fibroblasts (MEFs) treated with PES. We excluded the involvement of effector caspases, BAX and BAK, in causing PES-triggered cell death. Therefore, apoptosis was ruled out as the lethal mode of action of PES. Surprisingly, MEFs containing BAX were significantly protected from PES treatments. BAX overexpression in Bax-/- MEFs confirmed this pro-survival effect. Moreover, this protective effect required the ability of BAX to localise to mitochondrial membranes. Conversely, mitochondrial fusion induced by treatment with Mdivi-1 conferred increased resistance to MEFs subjected to PES treatment. The involvement of BAX in the regulation of mitochondrial dynamics has been reported. We propose the promotion of mitochondrial fusion by BAX to be the pro-survival function attributed to BAX.

URI

http://hdl.handle.net/10459.1/47849

DOI

https://doi.org/10.1016/j.canlet.2014.07.037

Is part of

Cancer Letters, 2014, vol. 354, num. 1, p. 115-121