Protective effects of glucocorticoids on taxol-induced cytotoxicity in human leukemia HL-60 cells.
Although the therapeutic actions of glucocorticoids are largely attributed to anti-inflammatory and immunosuppressive effects, they have been implicated in enhancing tissue and cellular protections. In this study, we examined whether glucocorticoids including dexamethasone (Dex) and hydroxycortisone could diminish the cytotoxic effects of anti-microtubule agents including taxol (paclitaxel), microtubule stabilizing agent, and colchicine, microtubule disrupting agent, on human leukemia HL-60 cells. Taxol or colchicine decreased the viability of HL-60 cells in a dose-dependent manner. However, micromolar concentrations of glucocorticoids rendered HL-60 cells resistant against the cytotoxic activity of anti-microtubule agents. Pretreatments of the glucocorticoids were more effective than simultaneous treatments with antimicrotuble agents. The fact that actinomycin D or cycloheximide reversed the cytoprotective effects of glucocorticoids on cytotoxicities in HL-60 cells induced by antimicrotuble agents suggests glucocorticoids cytoprotection might be mediated via newly synthesized protein. Collectively, these data showed that micromolar concentrations of dexamethasone or hydrocortisone could attenuate the cytotoxic effects of taxol or colchicine on human leukemia HL-60 cells via protein synthesis.
Pae
H O
HO
Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, Chonbug, Korea.
Yoo
J C
JC
Choi
B M
BM
Kim
T Y
TY
Chung
H T
HT
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D005938:Glucocorticoids; D003609:Dactinomycin; D003513:Cycloheximide; D017239:Paclitaxel; D003078:Colchicine