RasGAP-derived peptide 38GAP potentiates the cytotoxicity of cisplatin through inhibitions of Akt, ERK and NF-κB in colon carcinoma HCT116 cells.

Abstract

To increase the efficacy of currently used anti-cancer genotoxins, a combination use of different drugs is a potential new therapeutical tool. Here, we reported that a synthetic RasGAP-derived peptide 38GAP with RasGAP(301-326) and TAT penetration sequences could enhance the effect of chemotherapeutic agent CDDP in human colon carcinoma HCT116 cells. Our results showed that 38GAP significantly increased the CDDP-induced apoptosis in HCT116 cells. This synergistic effect was associated with abrogation of CDDP-induced G2/M arrest by down-regulations of phospho-Cdc2 and p21, and inhibitions of phospho-AKT, phospho-ERK and NF-κB. In animal models, 38GAP combined with CDDP significantly suppressed CT26 tumor growth, while 38GAP alone showed slight inhibitory effect. Our data suggest that 38GAP in combination with chemotherapeutics will become a potential therapeutic strategy for colon cancers.

• Authors: Hao Zhang, Shenghua Zhang, Hongwei He, Wuli Zhao, Kaihuan Ren, Jianhua Chen, Rong-guang Shao
• Journal: Cancer letters (Cancer Lett) Vol. 308 Issue 1 Pg. 62-70 (Sep 01 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21570766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• GTPase-Activating Proteins
• NF-kappa B
• Peptide Fragments
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• Cisplatin

Topics

• Amino Acid Sequence
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Apoptosis (drug effects)
• Cell Growth Processes (drug effects)
• Cisplatin (pharmacology)
• Colonic Neoplasms (drug therapy, genetics, metabolism, pathology)
• DNA Damage
• Down-Regulation (drug effects)
• Drug Synergism
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• GTPase-Activating Proteins (pharmacology)
• HCT116 Cells
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Molecular Sequence Data
• NF-kappa B (antagonists & inhibitors, metabolism)
• Peptide Fragments (pharmacology)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)