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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Clinical & Epidemiology Abstract 49
HEIGHTENED REDOX STATUS OF PRIMARY EFFUSION LYMPHOMA CELLS CAN BE
EXPLOITED THERAPEUTICALLY BY DECREASING RESISTANCE TO OXIDATIVE
STRESS
Darya Bubman 1 , Utthara Nayar 2 , Balasz Csernus 3 , Ilaria Guasparri 3 , Ethel Cesarman 3
1= Program in Pharmacology, Weill Cornell Graduate School of Medical Sciences, 2=
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of
Medical Sciences, 3= Department of Pathology and Laboratory Medicine, Weill Cornell
Medical College
Abstract
Intracellular reactive oxygen species (ROS) levels are maintained in a fine balance; high
levels can induce an oxidative stress response and cell death, while chronic moderately
high levels may promote neoplastic growth and proliferation. Specifically, a high level of
the superoxide (O2 - ) species is associated with cellular transformation. We have shown
that PEL cells have higher levels of ROS, particularly superoxide, than KSHV-negative
cells. Furthermore, we showed that vFLIP is responsible for these high levels of
superoxide, by both overexpression and knockdown approaches. PEL cells also express
high levels of superoxide dismutases (SODs), specifically MnSOD, which is probably
necessary for PEL cells to eliminate superoxide and avoid oxidative stress. We therefore
determined whether oxidative stress could be used as an approach for the treatment of
PEL. 2-Methoxyestradiol (2ME2), or Panzem (Entremed), is an endogenous metabolite of
estrogen that has antiangiogenic and antitumor effects, and is currently in early clinical
studies for a variety of neoplasms. While 2ME2 acts through multiple mechanisms of
action, these include inhibition of SOD activity and disruption of angiogenesis through the
inhibition of hypoxia inducible factor-1 alpha (HIF-1α), a protein required for
angiogenesis and cell survival under hypoxic and oxidative stress. We therefore treated
cells with 2ME2 in vitro, and demonstrated that PELs, but not normal lymphocytes, were
extremely sensitive to drug. We also determined whether this drug is effective in vivo, by
using a mouse PEL xenograft model with in vivo imaging, following oral administration of
clinically formulated 2ME2.
Presenting author Email: utn2001@med.cornell.edu
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