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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 996-1002
Chemopreventive Agent Resveratrol, a Natural Product Derived From
Grapes, Triggers CD95 Signaling-Dependent Apoptosis in Human Tumor
Cells
Marie-Véronique Clément,
Jayshreekumari L. Hirpara,
Sanaul-Haq Chawdhury, and
Shazib Pervaiz
From the Department of Physiology and Oncology Research Institute,
NUMI, National University of Singapore, Singapore.
Resveratrol, a constituent of grapes and other food products, has
been shown to prevent carcinogenesis in murine models. We report here
that resveratrol induces apoptotic cell death in HL60 human leukemia
cell line. Resveratrol-treated tumor cells exhibit a dose-dependent
increase in externalization of inner membrane phosphatidylserine and in
cellular content of subdiploid DNA, indicating loss of membrane
phospholipid asymmetry and DNA fragmentation. Resveratrol-induced cell
death is mediated by intracellular caspases as observed by the
dose-dependent increase in proteolytic cleavage of caspase substrate
poly (ADP-ribose) polymerase (PARP) and the ability of caspase
inhibitors to block resveratrol cytotoxicity. We also show that
resveratrol treatment enhances CD95L expression on HL60 cells, as well
as T47D breast carcinoma cells, and that resveratrol-mediated cell
death is specifically CD95-signaling dependent. On the contrary,
resveratrol treatment of normal human peripheral blood lymphocytes
(PBLs) does not affect cell survival for up to 72 hours, which
correlates with the absence of a significant change in either CD95 or
CD95L expression on treated PBLs. These data show specific involvement
of the CD95-CD95L system in the anti-cancer activity of resveratrol and
highlight the chemotherapeutic potential of this natural product, in
addition to its recently reported chemopreventive activity.
© 1998 by The American Society of Hematology.
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