CRM1 as a new therapeutic target for non-Hodgkin lymphoma.
The chromosomal region maintenance 1 (CRM1) may serve as a novel target for cancer treatment. Here, we investigated the anti non-Hodgkin lymphoma (NHL) activity of two novel CRM1 inhibitors (KPT-185 and KPT-276) in vitro and in vivo. KPT-185 displayed potent antiproliferative properties and induced cell-cycle arrest and apoptosis in several NHL cell lines and patients' tumor cells. The antitumor activity mainly consisted of inducing caspase cleavage and downregulating the expression of antiapoptotic proteins such as CRM1, nuclear factor-κB, and survivin. Furthermore, oral administration of KPT-276 significantly suppressed tumor growth in mice with Jeko-1 xenograft without any major toxic effects.
['Han|Xiaohong|X|', 'Wang|Jianfei|J|', 'Shen|Yinchen|Y|', 'Zhang|Ningning|N|', 'Wang|Shuai|S|', 'Yao|Jiarui|J|', 'Shi|Yuankai|Y|']
D000178:Acrylamides D000179:Acrylates D000818:Animals D000970:Antineoplastic Agents D020169:Caspases D059447:Cell Cycle Checkpoints D015536:Down-Regulation D015972:Gene Expression Regulation, Neoplastic D006801:Humans D019169:Jurkat Cells D028884:Karyopherins D008228:Lymphoma, Non-Hodgkin D051379:Mice D016688:Mice, Inbred NOD D016513:Mice, SCID D009363:Neoplasm Proteins D059748:Proteolysis D018160:Receptors, Cytoplasmic and Nuclear D013844:Thiazoles D014230:Triazoles D023041:Xenograft Model Antitumor Assays
CRM1 Non-Hodgkin lymphoma CRM1 inhibitor