Effects of desipramine on the cell cycle and apoptosis in Ca3/7 mouse skin squamous carcinoma cells.
Desipramine (DMI) has been reported to induce glucocorticoid receptor-mediated signal transduction in recent studies. It has been suggested that a non-glucocorticoid receptor signaling pathway might play an important role in skin squamous carcinoma Ca3/7 cells. The aim of this study was to investigate the growth inhibitory effects of DMI on Ca3/7 cells by evaluating the mRNA expression of genes related to apoptosis and cell cycle progression. Hoechst nuclear staining and DNA fragmentation assays were used to detect apoptosis, and the cell cycle was analyzed by flow cytometry. Apoptotic bodies in the nuclei of cells and DNA fragmentation were observed when the Ca3/7 cells were treated with 20 microM DMI for 24 h. Quantitative RT-PCR (reverse transcriptional-polymerase chain reaction) showed that DMI caused a decrease in Bcl-2 and survivin but not Bcl-xL gene expression and an increase in the expression of Bax, Apaf-1, caspase-3 and caspase-7 in a dose- and time-dependent manner. DMI also caused translocation of the apoptosis-inducing factor from the cytoplasm to the nucleus as well as cell cycle arrest in the Ca3/7 cells. Quantitative RT-PCR revealed that DMI decreased the expression of the PCNA gene and caused an increase in the expression of the p21 and p27 genes in the Ca3/7 cells. Our results showed that DMI inhibited the growth of Ca3/7 cells by inducing both apoptosis and cell cycle arrest.
Kinjo
Tatsuya
T
Division of Digestive and General Surgery, University of the Ryukyus Faculty of Medicine, Okinawa 903-0215, Japan.
Kowalczyk
Piotr
P
Kowalczyk
Magdalena
M
Walaszek
Zbigniew
Z
Slaga
Thomas J
TJ
Hanausek
Margaret
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*
D051033:Apoptosis Inducing Factor; D003891:Desipramine