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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

Tomohiro Kozako, Keisuke Sato, Yuichiro Uchida, Naho Kato, Akiyoshi Aikawa, Kentaro Ogata, Hidetoshi Kamimura, Haruna Uemura, Makoto Yoshimitsu, Kenji Ishitsuka, Yasuki Higaki, Hiroaki Tanaka, Shin-Ichiro Honda, etc.

Oncotarget. 2018 Jun 12;9(45):27645-27655.

PMID: 29963226

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 for ATL. This is the first evidence to demonstrate the cell growth-inhibitory effect of an autophagy inducer by caspase-dependent apoptosis and caspase-independent cell death via autophagy and endonuclease G in leukemic cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP315702999	STF-62247		315702-99-9	Price

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