title: N-acetyl-cysteine enhances growth in BCR-ABL-transformed cells.
abstract: N-acetyl-cysteine (NAC) has been reported to have anticancer properties such as counteractions against mutagens and prevention of tumor progression by scavenging reactive oxygen species (ROS). However, here we report that NAC can enhance the anchorage-independent growth of cells transformed by activated ABL tyrosine kinases or Ras. This effect was not dependent on loss of focal adhesion kinase activation. NAC rescued cell growth that was suppressed by heat shock protein (Hsp) 90 inhibitors possibly by chemical modification of their quinone moiety. NAC rendered Rat1/BCR-ABL cells resistance to a Ras inhibitor manumycin in soft agar colony formation. In the absence of Hsp90 inhibitors, NAC stimulated the activation of MAP kinase in BCR-ABL-transformed but not in the parental Rat1 cells. We propose that NAC should be used carefully in cancer treatment.
authors.affiliation: Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
authors.forename: QiGuo
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fujiko
authors.initials: F
authors.lastname: Tsukahara
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Maru
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016313:Genes, abl; D011905:Genes, ras; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology*; D016374:Oncogene Proteins v-abl; D011505:Protein-Tyrosine Kinases / Q000172:deficiency; D051381:Rats
chemical_list: D018841:HSP90 Heat-Shock Proteins; D016374:Oncogene Proteins v-abl; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; C496052:Ptk2 protein, rat; D000111:Acetylcysteine