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2‐deoxyglucose inhibits chemotheapeutic drug‐induced apoptosis in human monocytic leukemia U937 cells ith inhibition of c‐Jun N‐terminal kinase 1/stress‐activated protein kinase activation
Author(s) -
Haga Naomi,
Naito Mikihiko,
Seimiya Hiroyuki,
Tomida Akihiro,
Dong Jian,
Tsuruo Takashi
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980330)76:1<86::aid-ijc14>3.0.co;2-e
Subject(s) - u937 cell , deoxyglucose , ask1 , kinase , apoptosis , protein kinase a , chemistry , mitogen activated protein kinase kinase , microbiology and biotechnology , cancer research , biology , biochemistry
Human monocytic leukemia U937 cells undergo apoptosis when treated with antitumor drugs, such as etoposide, camptothecin and mitomycin C. The molecular mechanism of the drug‐induced apoptosis is not well understood. In this study, we found that 2‐deoxyglucose (2DG), an analog of D‐glucose and an inducer of glucose‐regulated stress, inhibited anticancer drug‐induced but not tumor necrosis factor‐alpha‐induced apoptosis of U937 cells. 2DG did not reduce initial cellular damage caused by etoposide, an inhibitor of topoisomerase II, suggesting that 2DG affected subsequent cellular responses involved in apoptosis. 2DG inhibited the etoposide‐induced activation of c‐Jun N‐terminal kinase 1/stress‐activated protein kinase (JNK1/SAPK) and the subsequent activation of CPP32, both of which are positive regulators for etoposide‐induced apoptosis of U937 cells. Our results indicate that 2DG inhibits apoptosis by blocking the signals from cellular DNA damage for JNK1/SAPK activation. Int. J. Cancer 76:86–90, 1998.© 1998 Wiley‐Liss, Inc.