In addition, HDAC inhibitors act in synergy with TRAIL by upregulating the mitochondrial pathway; downregulating NF-kβ and its gene products, such as cyclin D1, Bcl-2, Bcl-XL, VEGF, HIF-1a, IL6, IL8, MMP-2, and MMP-9; and upregulating the pro-apoptotic proteins Bax, Bak, and p21/CIP1 and TRAIL receptors DR4 and DR5 in cancer cells [108]. This evidence concerns the gene BCL2 and cancer.