Inhibition of tumor cell growth by Triton X-100 through specific effects on cell-cycle-regulatory components.
A cross-linked form of the detergent Triton X-100, called Triton WR-1339, has been shown to reduce the spread of tumor cells in laboratory animals. However, some of these effects were controversial, probably due to the use of different tumor cell lines and varying sites of injection. In order to better understand these processes, we have used Triton X-100 and performed a molecular analysis of its growth-inhibitory function. Using the T24 bladder carcinoma cell line, we have shown that treatment of cells with this detergent caused a potent antiproliferative effect resulting from the downregulation of the key cell cycle regulators, the cyclin-dependent kinases (CDKs). CDK activity was lost due to a twofold effect, the increased expression of the CDK inhibitors p21(Cip1) and p27(Kip1) in combination with the reduced expression of cyclin A, a regulatory CDK subunit that is essential for CDK function. Taken together, our results provide a molecular basis for the antiproliferative effects of the Triton detergent, namely its differential effects on various parts of the cell cycle machinery.
Picache
Esther R
ER
Department of Molecular Microbiology and Immunology, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90089-9094, USA.
Hassanieh
Loubna
L
Broek
Daniel
D
Schönthal
Axel H
AH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003902:Detergents / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000473:pathology*; D017830:Octoxynol / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D003902:Detergents; D012333:RNA, Messenger; D011092:Polyethylene Glycols; D017830:Octoxynol; C016811:tyloxapol