Piperlongumine and some of its analogs inhibit selectively the human immunoproteasome over the constitutive proteasome

• Autor(a) principal: Bosc, Elodie
• Data de Publicação: 2018
• Outros Autores: Nastri, Jhennifer [UNESP], Lefort, Valérie, Valli, Marilia [UNESP], Contiguiba, Fernando, Pioli, Renan, Furlan, Maysa [UNESP], Bolzani, Vanderlan da Silva [UNESP], El Amri, Chahrazade, Reboud-Ravaux, Michèle
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.bbrc.2018.01.100; http://hdl.handle.net/11449/175807
• topic: Immunoproteasome; Piperlogumine; Piperlongumine analogs; Proteasome

The natural small molecule piperlongumine A is toxic selectively to cancer cells in vitro and in vivo. This toxicity has been correlated with cancer cell ROS, DNA damage and apoptotic cell death increases. We demonstrate here a new mechanistic property of piperlongumine: it inhibits selectively human immunoproteasome with no noticeable inhibition of human constitutive proteasome. This result suggests that immunoproteasome inhibition, a mechanism independent of ROS elevation, may also partly play a role in the anticancer effects observed with piperlongumine. Structure-activity relationships of piperlongumine analogs suggest that the lactam (piperidonic) ring of piperlongumine A may be replaced by the linear olefin –NHCO-CH2=CH2 to improve both in vitro inhibitory efficiency against immunoproteasome and cellular toxicity.