Ceramides promote apoptosis for virus-infected lymphoma cells through induction of ceramide synthases and viral lytic gene expression

Oncotarget
Lu DaiChris Parsons

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for several human cancers including primary effusion lymphoma (PEL), a rapidly progressive malignancy arising preferentially in immunocompromised patients. With conventional chemotherapy, PEL continues to portend high mortality, dictating the development of novel therapeutic strategies. Sphingosine kinase 2 (SphK2) represents a key gatekeeper for sphingolipid metabolism, responsible for conversion of ceramides to sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to intracellular accumulation of ceramides and induces apoptosis for KSHV-infected PEL cells, while suppressing tumor progression in vivo. In the current study, we sought to determine whether specific ceramide/dh-ceramide species and related ceramide synthases (CerS) impact viability for KSHV-infected PEL cells during targeting of SphK2. We found that several specific ceramide and dihydro(dh)-ceramide species and their associated CerS reduce PEL survival and tumor expansion in vitro and in vivo. Moreover, we found that dhC16-Cer induces PEL apoptosis in part through activation of KSHV lytic gene expression. These dat...Continue Reading

References

Jul 11, 2006·Methods : a Companion to Methods in Enzymology·Jacek BielawskiAlicja Bielawska
Jan 8, 2013·Advances in Cancer Research·Sahar A Saddoughi, Besim Ogretmen

❮ Previous
Next ❯

Citations

Apr 15, 2017·Oncotarget·Bao Quoc LamZhiqiang Qin
Feb 1, 2019·Journal of Virology·Nadia SoudaniHassan Zaraket
May 10, 2016·F1000Research·Nathan J Dissinger, Blossom Damania
Dec 27, 2017·International Journal of Cancer. Journal International Du Cancer·Lu DaiZhiqiang Qin
Aug 26, 2019·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Preeti GuptaMd Imtaiyaz Hassan
Dec 29, 2015·Biochemical Pharmacology·Io-Guané RiveraAntonio Gomez-Muñoz
Sep 19, 2021·The FEBS Journal·Kwun Wah WenBlossom Damania

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
flow cytometry
transfection
PCR

Software Mentioned

iQ5
SPSS
CellSense
Excel

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.