title: Geranylgeranylacetone attenuates cisplatin-induced reductions in cell viability by suppressing the elevation of intracellular p53 content without heat shock protein induction.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Motofusa
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D019610:Cytoprotection; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D020011:Protective Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3; D002945:Cisplatin; C031049:geranylgeranylacetone