The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells

Tae Wook Chung, Hee Jung Choi, Seok Jo Kim, Choong Hwan Kwak, Kwon Ho Song, Un Ho Jin, Young Chae Chang, Hyeun Wook Chang, Young Choon Lee, Ki Tae Ha, Cheorl Ho Kim

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere92786
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 14 2014

Fingerprint

G(M3) Ganglioside
gangliosides
cisplatin
colorectal neoplasms
Colonic Neoplasms
Cisplatin
apoptosis
Cells
Apoptosis
HCT116 Cells
reactive oxygen species
Reactive Oxygen Species
cells
Gangliosides
neoplasm cells
Mitochondria
DNA fragmentation
Cell proliferation
DNA Fragmentation
small interfering RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chung, T. W., Choi, H. J., Kim, S. J., Kwak, C. H., Song, K. H., Jin, U. H., ... Kim, C. H. (2014). The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. PLoS One, 9(5), [e92786]. https://doi.org/10.1371/journal.pone.0092786
Chung, Tae Wook ; Choi, Hee Jung ; Kim, Seok Jo ; Kwak, Choong Hwan ; Song, Kwon Ho ; Jin, Un Ho ; Chang, Young Chae ; Chang, Hyeun Wook ; Lee, Young Choon ; Ha, Ki Tae ; Kim, Cheorl Ho. / The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. In: PLoS One. 2014 ; Vol. 9, No. 5.
@article{224e3270cda44c87a80718d0a6d0b7bb,
title = "The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells",
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.",
author = "Chung, {Tae Wook} and Choi, {Hee Jung} and Kim, {Seok Jo} and Kwak, {Choong Hwan} and Song, {Kwon Ho} and Jin, {Un Ho} and Chang, {Young Chae} and Chang, {Hyeun Wook} and Lee, {Young Choon} and Ha, {Ki Tae} and Kim, {Cheorl Ho}",
year = "2014",
month = "5",
day = "14",
doi = "10.1371/journal.pone.0092786",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

Chung, TW, Choi, HJ, Kim, SJ, Kwak, CH, Song, KH, Jin, UH, Chang, YC, Chang, HW, Lee, YC, Ha, KT & Kim, CH 2014, 'The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells', PLoS One, vol. 9, no. 5, e92786. https://doi.org/10.1371/journal.pone.0092786

The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. / Chung, Tae Wook; Choi, Hee Jung; Kim, Seok Jo; Kwak, Choong Hwan; Song, Kwon Ho; Jin, Un Ho; Chang, Young Chae; Chang, Hyeun Wook; Lee, Young Choon; Ha, Ki Tae; Kim, Cheorl Ho.

In: PLoS One, Vol. 9, No. 5, e92786, 14.05.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells

AU - Chung, Tae Wook

AU - Choi, Hee Jung

AU - Kim, Seok Jo

AU - Kwak, Choong Hwan

AU - Song, Kwon Ho

AU - Jin, Un Ho

AU - Chang, Young Chae

AU - Chang, Hyeun Wook

AU - Lee, Young Choon

AU - Ha, Ki Tae

AU - Kim, Cheorl Ho

PY - 2014/5/14

Y1 - 2014/5/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84901361141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901361141&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0092786

DO - 10.1371/journal.pone.0092786

M3 - Article

C2 - 24829158

AN - SCOPUS:84901361141

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e92786

ER -