The small molecule STF-62247 induces apoptotic and autophagic cell death in leukemic cells.

The small molecule STF-62247 induces apoptotic and autophagic cell death in leukemic cells. Oncotarget. 2018 Jun 12;9(45):27645-27655 Authors: Kozako T, Sato K, Uchida Y, Kato N, Aikawa A, Ogata K, Kamimura H, Uemura H, Yoshimitsu M, Ishitsuka K, Higaki Y, Tanaka H, Honda SI, Soeda S Abstract Adult T cell leukemia/lymphoma (ATL) is an aggressive malignant T cell disease caused by human T cell leukemia virus-I (HTLV-1). Treatment outcomes for aggressive subtypes of ATL remain poor, with little improvement in overall survival since HTLV-1 was discovered. Therefore, new therapeutic strategies for ATL are required. STF-62247 induces autophagy and selectively kills renal cell carcinoma without apoptotic cell death. Here, we demonstrate that STF-62247 reduced cell viability and resulted in autophagosome accumulation and autophagy in leukemic cell lines (S1T, MT-2, and Jurkat). Interestingly, STF-62247 induced apoptosis in HTLV-1-infected cell lines (S1T and MT-2), as indicated by DNA fragmentation and caspase activation, but not in non-HTLV-1-infected Jurkat cells; a caspase inhibitor did not prevent this caspase-associated cell death. STF-62247 also increased nuclear endonuclease G levels. Furthermore, STF-62247 reduced cell viability and increased the number of apoptotic cells in peripheral blood mononuclear cells collected from patients with acute ATL, which has a poor prognosis. Therefore, STF-62247 may have novel therapeutic potential...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research