Desipramine-induced apoptosis in human PC3 prostate cancer cells: Activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation

Chang, Hong-Chiang; Huang, Chorng-Chih; Huang, Chengwei; Cheng, Jin‐Shiung; Liu, Shiuh-In; Tsai, Jeng-Yu; Chang, Hong‐Tai; Huang, Jong‐Khing; Chou, Chiang-Ting; Jan, Chung‐Ren

doi:10.1016/j.tox.2008.05.010

Cited by 35 publications

(26 citation statements)

References 42 publications

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“…These findings are in agreement with previous studies which found that DMI inhibited cell proliferation and induced apoptosis in osteosarcoma cells, prostate cancer, colon cancer, renal tubular and glioma cells (14,15,(26)(27)(28)(29) and caused cell cycle arrest in colon cancer cells (13). In this study, we found a decrease in mRNA expression of Bcl-2 and survivin.…”

Section: Discussionsupporting

confidence: 94%

Effects of desipramine on the cell cycle and apoptosis in Ca3/7 mouse skin squamous carcinoma cells

Hanausek,¹

2010

Int J Mol Med

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Abstract. 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 μM 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 timedependent 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.

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Section: Discussionsupporting

confidence: 94%

Effects of desipramine on the cell cycle and apoptosis in Ca3/7 mouse skin squamous carcinoma cells

Hanausek,¹

2010

Int J Mol Med

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“…The interaction between amitriptyline and HDAC7 was decomposed by using the Molecular Mechanics-Generalized Born Surface Area (MM/GBSA) decomposition procedure implemented in AMBER10 (Gohlke et al, 2003;Chang et al, 2008). We calculated van der Waals (⌬E vdw ), electrostatic (⌬E ele ), and desolvation (⌬G GB ϩ ⌬G SA ) energies between ligand and each of the protein residues.…”

Section: Methodsmentioning

confidence: 99%

The Tricyclic Antidepressant Amitriptyline Inhibits d-Cyclin Transactivation and Induces Myeloma Cell Apoptosis by Inhibiting Histone Deacetylases: In Vitro and In Silico Evidence

Mao

Hou²,

Cao³

et al. 2011

Mol Pharmacol

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Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyeloma activity by inhibiting histone deacetylases (HDACs). Amitriptyline markedly decreased cyclin D2 promoter-driven luciferase activity, reduced cyclin D2 expression, and arrested cells at the G 0 /G 1 phase of the cell cycle. Amitriptyline-induced apoptosis was confirmed by Annexin V staining, and cleavage of caspase-3 and poly(ADP-ribose) polymerase-1. D-Cyclin expression is reported to be epigenetically regulated by histone acetylation. Thus, we examined the effects of amitriptyline on histone 3 (H3) acetylation and demonstrated that amitriptyline increased acetylation of H3 and expression of p27 and p21. Further studies indicated that amitriptyline interfered with HDAC function by down-regulation of HDAC3, -6, -7, and -8, but not HDAC2, and by interacting with HDAC7. Molecular docking analysis and molecular dynamics simulations revealed that amitriptyline bound to HDAC7 and formed strong van der Waals interactions with five residues of HDAC7, including Phe162, His192, Phe221, Leu293, and His326, thus inhibiting HDAC activity. Therefore, we found that amitriptyline inhibited cyclin D2 transactivation and HDAC activity and could be a promising treatment for multiple myeloma.

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“…PC3 cells have characteristics similar to human prostate cells and have been used as a model for research on the human prostate (Rodan et al, 1983). Many endogenous and exogenous reagents can stimulate PC3 cells by evoking a [Ca 2+ ] i rise, such as desipramine (Chang et al, 2008), safrole (Chang et al, 2006), and histamine (Lee et al, 2001). The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca 2+ store is an important Ca 2+ store that releases Ca 2+ into the cytosol when cells are stimulated by endogenous ligands, such as histamine (Lee et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca 2+ store is an important Ca 2+ store that releases Ca 2+ into the cytosol when cells are stimulated by endogenous ligands, such as histamine (Lee et al, 2001). But, exogenous ligands can release Ca 2+ from inositol IP3insensitive stores (Chang et al, 2006(Chang et al, , 2008.…”

Section: Introductionmentioning

confidence: 99%

Effect of celecoxib on Ca²⁺handling and viability in human prostate cancer cells (PC3)

Wang¹,

Lin²,

Chou³

et al. 2011

Drug and Chemical Toxicology

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Celecoxib has been shown to have an antitumor effect in previous studies, but the mechanisms are unclear. Ca(2+) is a key second messenger in most cells. The effect of celecoxib on cytosolic free Ca(2+) concentrations ([Ca(2+)](i)) in human suspended PC3 prostate cancer cells was explored by using fura-2 as a fluorescent dye. Celecoxib at concentrations between 5 and 30 μM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). Celecoxib-induced Ca(2+) influx was not blocked by L-type Ca(2+) entry inhibitors or protein kinase C/A modulators [phorbol 12-myristate 13-acetate (PMA), GF109203X, H-89], but was inhibited by the phospholipase A(2) inhibitor, aristolochic acid. In Ca(2+)-free medium, 30 μM of celecoxib failed to induce a [Ca(2+)](i) rise after pretreatment with thapsigargin (an endoplasmic reticulum [ER] Ca(2+) pump inhibitor). Conversely, pretreatment with celecoxib inhibited thapsigargin-induced Ca(2+) release. Inhibition of phospholipase C with U73122 did not change celecoxib-induced [Ca(2+)](i) rises. Celecoxib induced slight cell death in a concentration-dependent manner, which was enhanced by chelating cytosolic Ca(2+) with BAPTA. Collectively, in PC3 cells, celecoxib induced [Ca(2+)](i) rises by causing phospholipase C-independent Ca(2+) release from the ER and Ca(2+) influx via non-L-type, phospholipase A(2)-regulated Ca(2+) channels. These data may contribute to the understanding of the effect of celecoxib on prostate cancer cells.

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Desipramine-induced apoptosis in human PC3 prostate cancer cells: Activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation

Cited by 35 publications

References 42 publications

Effects of desipramine on the cell cycle and apoptosis in Ca3/7 mouse skin squamous carcinoma cells

Effects of desipramine on the cell cycle and apoptosis in Ca3/7 mouse skin squamous carcinoma cells

The Tricyclic Antidepressant Amitriptyline Inhibits d-Cyclin Transactivation and Induces Myeloma Cell Apoptosis by Inhibiting Histone Deacetylases: In Vitro and In Silico Evidence

Effect of celecoxib on Ca²⁺handling and viability in human prostate cancer cells (PC3)

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Desipramine-induced apoptosis in human PC3 prostate cancer cells: Activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation

Cited by 35 publications

References 42 publications

Effects of desipramine on the cell cycle and apoptosis in Ca3/7 mouse skin squamous carcinoma cells

Effects of desipramine on the cell cycle and apoptosis in Ca3/7 mouse skin squamous carcinoma cells

The Tricyclic Antidepressant Amitriptyline Inhibits d-Cyclin Transactivation and Induces Myeloma Cell Apoptosis by Inhibiting Histone Deacetylases: In Vitro and In Silico Evidence

Effect of celecoxib on Ca2+handling and viability in human prostate cancer cells (PC3)

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Effect of celecoxib on Ca²⁺handling and viability in human prostate cancer cells (PC3)