RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells
To increase the efficacy of currently used anti-cancer genotoxins, one of the current efforts is to find agents that can sensitize cancer cells to genotoxins so that the efficacious doses of genotoxins can be lowered to reduce deleterious side-effects. In this study, we reported that a synthetic Ras...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-04-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383514000240 |
| _version_ | 1818206083671392256 |
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| author | Hao Zhang Shenghua Zhang Hongwei He Caixia Zhang Yi Chen Dongke Yu Jianhua Chen Rongguang Shao |
| author_facet | Hao Zhang Shenghua Zhang Hongwei He Caixia Zhang Yi Chen Dongke Yu Jianhua Chen Rongguang Shao |
| author_sort | Hao Zhang |
| collection | DOAJ |
| description | To increase the efficacy of currently used anti-cancer genotoxins, one of the current efforts is to find agents that can sensitize cancer cells to genotoxins so that the efficacious doses of genotoxins can be lowered to reduce deleterious side-effects. In this study, we reported that a synthetic RasGAP-derived peptide GAP159 could enhance the effect of chemotherapeutic agent cisplatin (CDDP) in human colon carcinoma HCT116 cells. Our results showed that GAP159 significantly increased the CDDP-induced cytotoxicity and apoptosis in HCT116 cells. This synergistic effect was associated with the inhibitions of phospho-AKT, phospho-ERK and NF-κB. In mouse colon tumor CT26 animal models, GAP159 combined with CDDP significantly suppressed CT26 tumor growth, and GAP159 alone showed slight inhibitory effect. Our data suggests that co-treatment of GAP159 and chemotherapeutics will become a potential therapeutic strategy for colon cancers. |
| first_indexed | 2024-12-12T04:07:23Z |
| format | Article |
| id | doaj.art-90089208ab934971b9e7c84c296b6195 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 2211-3843 |
| language | English |
| last_indexed | 2024-12-12T04:07:23Z |
| publishDate | 2014-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-90089208ab934971b9e7c84c296b61952022-12-22T00:38:43ZengElsevierActa Pharmaceutica Sinica B2211-38352211-38432014-04-014212813410.1016/j.apsb.2014.02.004RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cellsHao Zhang0Shenghua Zhang1Hongwei He2Caixia Zhang3Yi Chen4Dongke Yu5Jianhua Chen6Rongguang Shao7Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaWuhan KatyGen Pharmaceuticals, Inc., Wuhan 430074, ChinaInstitute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaTo increase the efficacy of currently used anti-cancer genotoxins, one of the current efforts is to find agents that can sensitize cancer cells to genotoxins so that the efficacious doses of genotoxins can be lowered to reduce deleterious side-effects. In this study, we reported that a synthetic RasGAP-derived peptide GAP159 could enhance the effect of chemotherapeutic agent cisplatin (CDDP) in human colon carcinoma HCT116 cells. Our results showed that GAP159 significantly increased the CDDP-induced cytotoxicity and apoptosis in HCT116 cells. This synergistic effect was associated with the inhibitions of phospho-AKT, phospho-ERK and NF-κB. In mouse colon tumor CT26 animal models, GAP159 combined with CDDP significantly suppressed CT26 tumor growth, and GAP159 alone showed slight inhibitory effect. Our data suggests that co-treatment of GAP159 and chemotherapeutics will become a potential therapeutic strategy for colon cancers.http://www.sciencedirect.com/science/article/pii/S2211383514000240GAP159CDDPChemosensitizationColon cancerApoptosis |
| spellingShingle | Hao Zhang Shenghua Zhang Hongwei He Caixia Zhang Yi Chen Dongke Yu Jianhua Chen Rongguang Shao RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells Acta Pharmaceutica Sinica B GAP159 CDDP Chemosensitization Colon cancer Apoptosis |
| title | RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells |
| title_full | RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells |
| title_fullStr | RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells |
| title_full_unstemmed | RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells |
| title_short | RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells |
| title_sort | rasgap derived peptide gap159 enhances cisplatin induced cytotoxicity and apoptosis in hct116 cells |
| topic | GAP159 CDDP Chemosensitization Colon cancer Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2211383514000240 |
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