The Ganglioside GM3 Is Associated with Cisplatin-Induced Apoptosis in Human Colon Cancer Cells

Title
The Ganglioside GM3 Is Associated with Cisplatin-Induced Apoptosis in Human Colon Cancer Cells
Author(s)
장현욱정태욱[정태욱]최희중[최희중]김석조[김석조]곽충환[곽충환]송권호[송권호]진언호[진언호]장영채[장영채]이영춘[이영춘]하기태[하기태]김철호[김철호]
Keywords
PLASMA-MEMBRANE; SIGNAL-TRANSDUCTION; HL-60 CELLS; RAT-LIVER; ACTIVATION; DEATH; 12-LIPOXYGENASE; EXPRESSION; INDUCTION; PATHWAY
Issue Date
201405
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.9, no.5
Abstract
Cisplatin (cis-diamminedichloroplatinum, CDDP) is a well-known chemotherapeutic agent for the treatment of several cancers. However, the precise mechanism underlying apoptosis of cancer cells induced by CDDP remains unclear. In this study, we show mechanistically that CDDP induces GM3-mediated apoptosis of HCT116 cells by inhibiting cell proliferation, and increasing DNA fragmentation and mitochondria-dependent apoptosis signals. CDDP induced apoptosis within cells through the generation of reactive oxygen species (ROS), regulated the ROS-mediated expression of Bax, Bcl-2, and p53, and induced the degradation of the poly (ADP-ribosyl) polymerase (PARP). We also checked expression levels of different gangliosides in HCT116 cells in the presence or absence of CDDP. Interestingly, among the gangliosides, CDDP augmented the expression of only GM3 synthase and its product GM3. Reduction of the GM3 synthase level through ectopic expression of GM3 small interfering RNA (siRNA) rescued HCT116 cells from CDDP-induced apoptosis. This was evidenced by inhibition of apoptotic signals by reducing ROS production through the regulation of 12-lipoxigenase activity. Furthermore, the apoptotic sensitivity to CDDP was remarkably increased in GM3 synthase-transfected HCT116 cells compared to that in controls. In addition, GM3 synthase-transfected cells treated with CDDP exhibited an increased accumulation of intracellular ROS. These results suggest the CDDP-induced oxidative apoptosis of HCT116 cells is mediated by GM3.
URI
http://hdl.handle.net/YU.REPOSITORY/32343http://dx.doi.org/10.1371/journal.pone.0092786
ISSN
1932-6203
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약학대학 > 약학부 > Articles
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