RRC ID 67344
Author Hasegawa M, Ishiguro K, Ando T, Goto H.
Title Geranylgeranylacetone attenuates cisplatin-induced reductions in cell viability by suppressing the elevation of intracellular p53 content without heat shock protein induction.
Journal Nagoya J Med Sci
Abstract Geranylgeranylacetone (GGA) was originally used as an anti-ulcer drug to protect gastric mucosa from various stresses, and it is also known to induce heat shock proteins (HSPs), especially HSP70. However, it remains unclear how GGA affects cellular functions in the presence of anti-cancer drugs. We investigated the effects of GGA on cellular viability, caspase-3 activation, HSP induction and p53 content in the presence of cisplatin (CDDP). Rat intestinal epithelium-derived IEC-18 cells and human colon cancer-derived CW-2 cells were incubated with GGA in the presence of CDDP, and we observed that GGA attenuated CDDP-induced viability reductions. GGA also suppressed CDDP-induced caspase-3 activation. However, GGA induced neither HSP70 nor GRP78 expression in the presence of CDDP. We found that GGA suppressed the CDDP-induced elevation of intracellular p53 content. In conclusion, GGA attenuates viability reductions and caspase-3 activation in CDDP-treated cells by suppressing the elevation of intracellular p53 content without HSP induction.
Volume 74(1-2)
Pages 123-31
Published 2012-2-1
PMID 22515118
PMC PMC4831257
MeSH Animals Antineoplastic Agents / toxicity* Caspase 3 / metabolism Cell Line, Tumor Cell Survival / drug effects Cisplatin / toxicity* Cytoprotection Diterpenes / pharmacology* Dose-Response Relationship, Drug Endoplasmic Reticulum Chaperone BiP Enzyme Activation HSP70 Heat-Shock Proteins / metabolism Heat-Shock Proteins / metabolism* Humans Intestinal Mucosa / drug effects* Intestinal Mucosa / metabolism Intestinal Mucosa / pathology Protective Agents / pharmacology* Rats Time Factors Tumor Suppressor Protein p53 / metabolism*
IF 0.762
Human and Animal Cells CW-2(RCB0778)