Schemes of the opposing responses of p53 after lupulone treatment in SW620 and SW480 cells

Schemes of the opposing responses of p53 after lupulone treatment in SW620 and SW480 cells. (A) In SW620 cells, lupulone induced apoptosis by activating the extrinsic apoptotic signaling pathway involving TRAIL-DR4/DR5 receptors and caspases activation []. In these cells, p53 plays a proapoptotic role. Lupulone upregulated p53 transcription and protein expression; p53 accumulated in the nucleus, where it enhanced the transcription of TRAIL-DR5 gene, which amplified the apoptotic response triggered by lupulone. Inhibition of p53 by PFT-α caused only a limited decrease of cell death because TRAIL-DR4 receptor expression remained unaffected by p53 activation. (B) In SW480 cells, lupulone induced apoptosis by activating both the extrinsic and intrinsic (mitochondrial) apoptotic signaling pathways involving TRAIL-DR4/DR5 receptors and caspases activation [9]. As opposed to SW620 cells, p53 played the role of a survival factor in SW480 cells. Indeed, activation of p53 by lupulone caused a down-regulation of TRAIL-DR4 and -DR5 expression and a translocation of p53 from the nucleus to the cytosol associated with an up-regulation of the antiapoptotic Bcl-2 and Mcl-1 proteins favoring a protective effect on mitochondrial function. These prosurvival effects of p53 were reversed by PFT-α, which caused a blocking of p53 in the nucleus enhancing its proapoptotic effects.

Publication

p53 Activates Either Survival or Apoptotic Signaling Responses in Lupulone-Treated Human Colon Adenocarcinoma Cells and Derived Metastatic Cells. (2010) Virginie Lamy, et al. Transl Oncol. 2010 Oct;3(5):286-292. Figure: F7. Arabidopsis thaliana

Disease mentions