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Ghrelin induces apoptosis in colon adenocarcinoma cells via proteasome inhibition and autophagy induction

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Abstract

Ghrelin is a metabolism-regulating hormone recently investigated for its role in cancer survival and progression. Controversially, ghrelin may act as either anti-apoptotic or pro-apoptotic factor in different cancer cells, suggesting that the effects are cell type dependent. Limited data are currently available on the effects exerted by ghrelin on intracellular proteolytic pathways in cancer. Both the lysosomal and the proteasomal systems are fundamental in cellular proliferation and apoptosis regulation. With the aim of exploring if the proteasome and autophagy may be possible targets of ghrelin in cancer, we exposed human colorectal adenocarcinoma cells to ghrelin. Preliminary in vitro fluorimetric assays evidenced for the first time a direct inhibition of 20S proteasomes by ghrelin, particularly evident for the trypsin-like activity. Moreover, 1 μM ghrelin induced apoptosis in colorectal adenocarcinoma cells by inhibiting the ubiquitin–proteasome system and by activating autophagy, with p53 having an “interactive” role.

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  1. School of Biosciences and Biotechnology, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Macerata, Italy

    Laura Bonfili, Massimiliano Cuccioloni, Valentina Cecarini, Matteo Mozzicafreddo, Francesco Alessandro Palermo, Paolo Cocci, Mauro Angeletti & Anna Maria Eleuteri

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  1. Laura Bonfili
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  2. Massimiliano Cuccioloni
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Bonfili, L., Cuccioloni, M., Cecarini, V. et al. Ghrelin induces apoptosis in colon adenocarcinoma cells via proteasome inhibition and autophagy induction. Apoptosis 18, 1188–1200 (2013). https://doi.org/10.1007/s10495-013-0856-0

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