The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells.
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 apopt...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4020741?pdf=render |
| _version_ | 1828386651778318336 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Tae-Wook Chung |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:40:55Z |
| format | Article |
| id | doaj.art-1efc02fb1b774850bc9a68c5031c1f18 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T05:40:55Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1efc02fb1b774850bc9a68c5031c1f182022-12-22T02:00:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9278610.1371/journal.pone.0092786The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells.Tae-Wook ChungHee-Jung ChoiSeok-Jo KimChoong-Hwan KwakKwon-Ho SongUn-Ho JinYoung-Chae ChangHyeun Wook ChangYoung-Choon LeeKi-Tae HaCheorl-Ho KimCisplatin (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.http://europepmc.org/articles/PMC4020741?pdf=render |
| spellingShingle | 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 The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. PLoS ONE |
| title | The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. |
| title_full | The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. |
| title_fullStr | The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. |
| title_full_unstemmed | The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. |
| title_short | The ganglioside GM3 is associated with cisplatin-induced apoptosis in human colon cancer cells. |
| title_sort | ganglioside gm3 is associated with cisplatin induced apoptosis in human colon cancer cells |
| url | http://europepmc.org/articles/PMC4020741?pdf=render |
| work_keys_str_mv | AT taewookchung thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT heejungchoi thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT seokjokim thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT choonghwankwak thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT kwonhosong thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT unhojin thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT youngchaechang thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT hyeunwookchang thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT youngchoonlee thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT kitaeha thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT cheorlhokim thegangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT taewookchung gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT heejungchoi gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT seokjokim gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT choonghwankwak gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT kwonhosong gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT unhojin gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT youngchaechang gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT hyeunwookchang gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT youngchoonlee gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT kitaeha gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells AT cheorlhokim gangliosidegm3isassociatedwithcisplatininducedapoptosisinhumancoloncancercells |