Geranylgeranylacetone Attenuates Cisplatin-induced Reductions in Cell Viability by Suppressing the Elevation of Intracellular P53 Content without Heat Shock Protein Induction
نویسندگان
چکیده
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.
منابع مشابه
Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation
Recognition of the molecular mechanisms of cAMP action against DNA damage-induced apoptosis can be useful to improve the efficacy of DNA damaging therapeutic agents. Considering the critical role of bcl-2-associated death promoter (BAD) and p53 proteins in DNA damage -induced apoptosis, the aim of this study was to assess the effect of cAMP-elevating agents on these proteins in doxorubicin-trea...
متن کاملP-11: Evaluation of Heat Shock Protein A2 in Male Rats before and after Varicocele Induction
Background: Varicocele is a major cause of male infertility, as it may impair spermatogenesis through several distinct pathophysiological mechanisms including hypoxia, renal-adrenal reflux, hormonal dysfunction, autoimmunity, oxidative stress and hyperthermia. HSP70s are members of the heat shock protein (HSP) family, which are considered intracellular chaperones. Their expressions can increase...
متن کاملAnticancer effect of Artemisia extract and cisplatin on induction of apoptosis and inhibition of proliferation in A2780 human ovarian cancer
Cisplatin, as a chemotherapy drug, causes serious side effects in the advanced stages of the cancer. Recently, Artemisia has been considered for its bioactive compounds, anti-proliferative and anti-inflammatory effects. The aim of this study was to evaluate the anti-cancer and anti-metastatic effects of the methanolic extract of aerial organs of Artemisia and cisplatin, either alone or in combi...
متن کاملIncreased Cytotoxicity of Cisplatin in SK-MEL 28 Melanoma Cells upon Down-Regulation of Melanoma Inhibitor of Apoptosis Protein
Background: Malignant melanoma is a highly metastatic cutaneous cancer and typically refractory to chemotherapy. Deregulated apoptosis has been identified as a major cause of cancer drug resistance, and upregulated expression of the inhibitor of apoptosis protein melanom, an inhibitor of apoptosis (ML-IAP) is frequent in melanoma. Methods: Based on the conclusion that ML-IAP expression contribu...
متن کاملDown-Regulation of T Cell Function by Heat Shock-Induced Excretory Factor of Leishmania Major
Background: Despite demonstration of molecular and biochemical changes induced by heat shock on Leishmania, the immunological importance of such changes has not been elucidated. Objective: Studying the effect of two excretory factors prepared under heat shock and ambient temperature from Leishmania major on Balb/c splenocytes function. Methods: The parasites were cultured at 25°C and then sub...
متن کامل