Joan Gil. Full Professor 
University of Barcelona. Website
Faculty of Medicine and Health Sciences-IDIBELL. Department of Physiological Sciences. Campus de Bellvitge, 08907 Hospitalet de Llobregat, Barcelona, Spain
Reseach subject
AICAR and new prohibitin-binding compounds as proapoptotic agents for cancer therapy
Summary
In the last years our research has been focused on the mechanism of apoptosis induction in cancer cells. Importantly, we have described two new proapoptotic drugs for the treatment of cancer: AICAR and trifluorinated thiazolines. First, we reported that AICAR induces apoptosis in chronic lymphocytic leukemia cells and other B-cell neoplasms. Although the target of AICAR remains unknown we described that the mechanism of action involves the induction of the proapoptotic Bcl-2 proteins Bim and Noxa. More recently, we have identified the protein prohibitin as a trifluorinated thiazolines-binding protein. The mechanism of apoptosis induction includes the presence of prohibitin and the induction of the proapoptotic Bcl-2 proteins Noxa. In addition, the pro-apoptotic effect of fluorizoline has been described in primary samples from patients with debut of acute myeloid leukemia (AML) and with chronic lymphocytic leukemia. Furthermore, fluorizoline synergized with ibrutinib and AICAR to induce apoptosis in chronic lymphocytic leukemia cells. Our next objectives are related with the elucidation of the mechanism of action of these two anticancer drugs.
Publications
- Pérez-Perarnau A, Preciado S, Palmeri CM, Moncunill-Massaguer C, Iglesias-Serret D, González-Gironès DM, MiguelM, Karasawa S,Sakamoto S, Cosialls AM, Rubio-Patiño C, Saura-Esteller J, Ramón R, Caja L, Fabregat I, Pons G, Handa, H, Albericio F, Gil J, Lavilla R. A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins. Angew. Chem. Int. Ed. 53:10150-10154, 2014.
- Moncunill-Massaguer, C, Pérez-Perarnau, A, Palmeri, CM, Saura-Esteller, J, Núñez-Vázquez, S, Cosialls, AM, González-Gironès, DM, Pomares, H, Korwitz, A, Preciado, S, Albericio, F, Lavilla, R, Pons, G, Langer, T, Iglesias-Serret, D, and Gil, J. A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation. Oncotarget, 6:41750-41765, 2015.
- Pomares, H, Palmeri, CM, Iglesias-Serret, D, Moncunill-Massaguer, C, Saura-Esteller, J, Núñez-Vázquez, S, Gamundi, E, Arnan, M, Preciado, S, Albericio, F, Lavilla, R, Pons, G, González-Barca, E, Cosialls, AM, and Gil, J. Targeting prohibitins induces apoptosis in acute myeloid leukemia cells. Oncotarget. 64987-65000, 2016.
- González-Girones DM , Moncunill-Massaguer, C, Iglesias-Serret, D, Cosialls, AM, Pérez-Perarnau A, Palmeri, CM, Rubio-Patiño, C, Pons, G, Villunger, A, Gil, J. AICAR induces Bax/Bak-dependent apoptosis through upregulation of the BH3-only proteins Bim and Noxa in mouse embryonic fibroblasts. Apoptosis 18:1008-1016, 2013
- Santidrián AF, González-Gironès DM, Iglesias-Serret D, Coll-Mulet L, Cosialls AM, de Frias M, Campàs C, González-Barca E, Alonso E, Labi V, Viollet B, Benito A, Pons G, Villunger A, Gil J. AICAR induces apoptosis independently of AMPK and p53 through upregulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood 116: 3023-3032, 2010.