ABC294640, A Novel Sphingosine Kinase 2 Inhibitor, Induces Oncogenic Virus-Infected Cell Autophagic Death and Represses Tumor Growth.

ABSTRACT: Kaposi sarcoma-associated herpes virus (KSHV) is the etiologic agent of several malignancies, including Kaposi sarcoma and primary effusion lymphoma (PEL), which preferentially arise in HIV⁺ patients and lack effective treatment. Sphingosine kinase 2 (SphK2) is a key factor within sphingolipid metabolism, responsible for the conversion of proapoptotic ceramides to antiapoptotic sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to the accumulation of intracellular ceramides and induces apoptosis in KSHV-infected primary endothelial cells and PEL tumor cells but not in uninfected cells. In this study, we found that ABC294640 induces autophagic death instead of apoptosis in a KSHV long-term-infect

SUBMITTER: Dai L 

PROVIDER: S-EPMC5716930 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature