Limits...
RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells.

Zhang H, Zhang S, He H, Zhang C, Chen Y, Yu D, Chen J, Shao R - Acta Pharm Sin B (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

GAP159 enhances CDDP induced apoptosis. A: Co-treatment of GAP159 and CDDP induced apoptosis detected by TUNEL assay; B: quantification of TUNEL positive cells (⁎P<0.05 vs Control, #P<0.05 vs CDDP); C: the changes of caspase-3/7 activity in GAP159 and/or CDDP treated cells. The results are mean±SD of three individual experiments.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4590723&req=5

f0015: GAP159 enhances CDDP induced apoptosis. A: Co-treatment of GAP159 and CDDP induced apoptosis detected by TUNEL assay; B: quantification of TUNEL positive cells (⁎P<0.05 vs Control, #P<0.05 vs CDDP); C: the changes of caspase-3/7 activity in GAP159 and/or CDDP treated cells. The results are mean±SD of three individual experiments.

Mentions: To determine whether GAP159 potentiated CDDP-induced apoptosis, we employed TUNEL staining assay (Fig. 3A). As shown in Fig. 3B, the percentage of TUNEL positive cells is increased from 1.1% in control cells to 6.7% and 12.6% in GAP159-treated cells. GAP159 also increased CDDP-induced TUNEL positive cells from 3.8% to 22.7% and 34.7% (Fig. 3B). This result is confirmed by caspase-3/7 activity assay, which showed GAP159 markedly enhanced CDDP induced caspase-3/7 activities (Fig. 3C). Taken together, the results indicate that GAP159 enhances CDDP-induced apoptosis.


RasGAP-derived peptide GAP159 enhances cisplatin-induced cytotoxicity and apoptosis in HCT116 cells.

Zhang H, Zhang S, He H, Zhang C, Chen Y, Yu D, Chen J, Shao R - Acta Pharm Sin B (2014)

GAP159 enhances CDDP induced apoptosis. A: Co-treatment of GAP159 and CDDP induced apoptosis detected by TUNEL assay; B: quantification of TUNEL positive cells (⁎P<0.05 vs Control, #P<0.05 vs CDDP); C: the changes of caspase-3/7 activity in GAP159 and/or CDDP treated cells. The results are mean±SD of three individual experiments.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590723&req=5

f0015: GAP159 enhances CDDP induced apoptosis. A: Co-treatment of GAP159 and CDDP induced apoptosis detected by TUNEL assay; B: quantification of TUNEL positive cells (⁎P<0.05 vs Control, #P<0.05 vs CDDP); C: the changes of caspase-3/7 activity in GAP159 and/or CDDP treated cells. The results are mean±SD of three individual experiments.
Mentions: To determine whether GAP159 potentiated CDDP-induced apoptosis, we employed TUNEL staining assay (Fig. 3A). As shown in Fig. 3B, the percentage of TUNEL positive cells is increased from 1.1% in control cells to 6.7% and 12.6% in GAP159-treated cells. GAP159 also increased CDDP-induced TUNEL positive cells from 3.8% to 22.7% and 34.7% (Fig. 3B). This result is confirmed by caspase-3/7 activity assay, which showed GAP159 markedly enhanced CDDP induced caspase-3/7 activities (Fig. 3C). Taken together, the results indicate that GAP159 enhances CDDP-induced apoptosis.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus