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Caffeine attenuates the action of amsacrine and etoposide in U‐937 cells by mechanisms which involve inhibition of RNA synthesis
Author(s) -
Pérez Concepción,
Pelayo Francisco,
Vilaboa Nuria E.,
Aller Patricio
Publication year - 1994
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/ijc.2910570619
Subject(s) - amsacrine , etoposide , topoisomerase , caffeine , rna , microbiology and biotechnology , dna , biology , mechanism of action , flow cytometry , chromatin , dna synthesis , podophyllotoxin , transcription (linguistics) , biochemistry , in vitro , chemistry , chemotherapy , stereochemistry , genetics , linguistics , philosophy , gene , endocrinology
Pulse treatments of U‐937 human promonocytic leukemia cells with the DNA topoisomerase‐II inhibitors 4′‐(9‐acridynilamino)methanesulfon‐ m ‐anisidide (amsacrine, m AMSA) or etoposide (VP‐16) caused growth inhibition, G 2 ‐arrest, increase in cell size and expression of differentiation markers. All these effects were greatly reduced by the presence of 5–10 mM caffeine. In addition, caffeine partially prevented the increase in the number of topoisomerase‐DNA cleavable complexes caused by the topoisomerase inhibitors, as determined by SDS/CIK precipitation assays; it caused chromatin condensation, as determined by flow cytometry assays, and interacted with m AMSA in solution, as suggested by spectrophotometric assays. Pulse treatment with caffeine greatly inhibited RNA synthesis but not DNA or protein synthesis, as indicated by labelled precursor incorporation assays. The transcription inhibitor 5,6‐dichloro‐1‐β‐D‐ribofuranosylbenzymidazole reduced the m AMSA‐ and VP‐16‐produced growth inhibition in a similar manner. It is concluded that RNA synthesis inhibition is one of the possible mechanisms by which caffeine protects cells from the action of topoisomerase‐II inhibitors. © 1994 Wiley‐Liss, Inc.