Journal article

Retinoic Acid/Alpha-Interferon Combination Inhibits Growth and Promotes Apoptosis in Mantle Cell Lymphoma through Akt-Dependent Modulation of Critical Targets

Jessica Dal Col, Katy Mastorci, Damiana Antonia Fae, Elena Muraro, Debora Martorelli, Giorgio Inghirami, Riccardo Dolcetti

CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2012

Abstract

Mantle cell lymphoma (MCL) is characterized by a profound deregulation of the mechanisms controlling cell-cycle progression and survival. We herein show that the combination of 9-cis-retinoic acid (RA) and IFN-α induces marked antiproliferative and proapoptotic effects in MCL cells through the modulation of critical targets. Particularly, IFN-α enhances RA-mediated G(0)-G(1) cell accumulation by downregulating cyclin D1 and increasing p27(Kip1) and p21(WAF1/Cip1) protein levels. Furthermore, RA/IFN-α combination also induces apoptosis by triggering both caspases-8 and -9 resulting in Bax and Bak activation. In particular, RA/IFN-α treatment downregulates the antiapoptotic Bcl-xL and Bfl-1 pr..

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