Fig. 5.

CDK4 activity is required for cell death induction after combined fatty acid synthase and proteasome inhibition. a Knockdown of either cyclin D1 or CDK4 antagonizes cell death as well as NOXA protein induction as efficient as knockdown of NOXA. MCL cell line Jeko-1 was transfected with siRNA targeting NOXA, CCND1, and CDK4. Twenty-four hours after transfection, cells were treated with 15 μM orlistat and 7 nM bortezomib. After 14 h, protein expression was analyzed (right) and cell death was assessed by AnnexinV-PI staining (left) 24 h post-treatment. b Co-treatment of bortezomib with orlistat is antagonized by palbociclib treatment. MCL cell line Jeko-1 was treated with 300 nM palbociclib and subsequently co-treated with 15 μM orlistat and 7 nM bortezomib. After 14 h, protein expression was analyzed (right) and cell death was assessed by AnnexinV-PI staining (left). Data represent means ± S.D. from three independent experiments