Radiology Commons^™

Bh3 Mimetic Abt-737 Sensitizes Colorectal Cancer Cells To Ixazomib Through Mcl-1 Downregulation And Autophagy Inhibition., Lifeng Yang, Juefeng Wan, Sheng Xiao, Darryll Barkhouse, Ji Zhu, Guichao Li, Bo Lu, Zhen Zhang

Department of Radiation Oncology Faculty Papers

The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances …