共查询到20条相似文献,搜索用时 12 毫秒
1.
Hsu SS Chen WC Lo YK Cheng JS Yeh JH Cheng HH Chen JS Chang HT Jiann BP Huang JK Jan CR 《Clinical and experimental pharmacology & physiology》2004,31(7):444-449
1. The effect of maprotiline, an antidepressant, on human prostate cells is unclear. In the present study, the effect of maprotiline on [Ca2+]i and growth in PC3 human prostate cancer cells was measured using the fluorescent dyes fura-2 and tetrazolium, respectively. 2. Maprotiline caused a rapid, concentration-dependent increase in [Ca2+]i (EC50 = 200 micromol/L). The maprotiline-induced [Ca2+]i increase was reduced by removal of extracellular Ca2+ or pretreatment with nicardipine. 3. The maprotiline-induced Mn2+ influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca2+ influx. 4. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca2+]i increase, after which the effects of maprotiline of increasing [Ca2+]i were abolished. In addition, pretreatment with maprotiline reduced a major portion of the thapsigargin-induced increase in [Ca2+]i. 5. U73122, an inhibitor of phospholipase C, abolished the ATP (but not maprotiline)-induced increase in [Ca2+]i. 6. Overnight incubation with 1-10 micromol/L maprotiline did not alter cell proliferation, although incubation with 30-50 micromol/L maprotiline decreased cell proliferation. 7, These findings suggest that maprotiline rapidly increases [Ca2+]i in human prostate cancer cells by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release and that it may modulate cell proliferation in a concentration-dependent manner. 相似文献
2.
Chih Chuan Pan Daih‐Huang Kuo Pochuen Shieh Fu‐An Chen Chun‐Chi Kuo Chung‐Ren Jan 《Drug development research》2010,71(2):120-126
The effect of the antidepressant paroxetine on cytosolic free Ca2+ concentrations ([Ca2+]i) in PC3 human prostate cancer cells is unclear. This study explored whether paroxetine changed basal [Ca2+]i levels in suspended PC3 cells by using fura‐2 as a Ca2+‐sensitive fluorescent dye. Paroxetine at concentrations between 10–150 µM increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was reduced by 55% by removing extracellular Ca2+. Paroxetine‐induced Ca2+ influx was inhibited by the store‐operated Ca2+ channel blockers econazole and SK&F96365, the phospholipase A2 inhibitor aristolochic acid, and protein kinase C modulators. In Ca2+‐free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin, 2,5‐di‐tert‐butylhydroquinone (BHQ), or cyclopiazonic acid (CPA) all abolished paroxetine‐induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 inhibited paroxetine‐induced [Ca2+]i rise by 80%. Collectively, in PC3 cells, paroxetine induced [Ca2+]i rise by causing phospholipase C‐dependent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store‐operated Ca2+ channels in a manner regulated by protein kinase C and phospholipase A2. Drug Dev Res, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
3.
Wei‐Chuan Liao Chiang‐Ting Chou Chun‐Chi Kuo Chih‐Chuan Pan Daih‐Huang Kuo Pochuen Shieh Jin‐Shiung Cheng Chung‐Ren Jan Chen‐Fu Shaw 《Drug development research》2011,72(4):330-336
The present study evaluated the effects of thimerosal, a vaccine preservative, on cytosolic free Ca2+ concentrations ([Ca2+]i) in human prostate cancer cells (PC3). Thimerosal (10–200 µM) increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Thimerosal‐induced Ca2+ influx was inhibited by econazole, SKF963656, the phospholipase A2 inhibitor aristolochic acid, and protein kinase C modulators [phorbol 12‐myristate 13‐acetate (PMA) and GF109203X]. In Ca2+‐free medium, a 200‐µM thimerosal‐induced [Ca2+]i rise was partly inhibited after pretreatment with 2,5‐di‐tert‐butylhydroquinone (BHQ) (an endoplasmic reticulum Ca2+ pump inhibitor). Thimerosal at 1–7 µM induced cell death in a concentration‐dependent manner that was not reversed when cytosolic Ca2+ was chelated with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA). Propidium iodide staining suggests that apoptosis played a role in the death. Collectively, in PC3 cells, thimerosal induced [Ca2+]i rise by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx via store‐operated Ca2+ channels in a manner regulated by protein kinase C and phospholipase A2. Thimerosal also induced cell death in a Ca2+‐independent apoptotic manner. Drug Dev Res 72: 330–336, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
4.
Jue-Long Wang Chiang-Ting Chou Wei-Zhe Liang Jeng-Hsien Yeh Chun-Chi Kuo Chao-Ying Lee 《Toxicology mechanisms and methods》2016,26(5):327-333
The phenolic compound 2,5-dimethylphenol is a natural product. 2,5-Dimethylphenol has been shown to affect rat hepatic and pulmonary microsomal metabolism. However, the effect of 2,5-dimethylphenol on Ca2+?signaling and cyotoxicity has never been explored in any culture cells. This study explored the effect of 2,5-dimethylphenol on cytosolic free Ca2+?levels ([Ca2+]i) and cell viability in PC3 human prostate cancer cells. 2,5-Dimethylphenol at concentrations between 500?μM and 1000?μM evoked [Ca2+]i rises in a concentration-dependent manner. This Ca2+?signal was inhibited by approximately half by the removal of extracellular Ca2+. 2,5-Dimethylphenol-induced Ca2+?influx was confirmed by Mn2+-induced quench of fura-2 fluorescence. Pretreatment with the protein kinase C (PKC) inhibitor GF109203X, nifedipine or the store-operated Ca2+?entry inhibitors (econazole or SKF96365) inhibited 2,5-dimethylphenol-induced Ca2+?signal in Ca2+-containing medium by ~30%. Treatment with the endoplasmic reticulum Ca2+?pump inhibitor thapsigargin in Ca2+-free medium abolished 2,5-dimethylphenol-induced [Ca2+]i rises. Conversely, treatment with 2,5-dimethylphenol abolished thapsigargin-induced [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 reduced 2,5-dimethylphenol-evoked [Ca2+]i rises by ~80%. 2,5-Dimethylphenol killed cells at concentrations of 350–1000?μM in a concentration-dependent fashion. Chelation of cytosolic Ca2+?with 1,2-bis(2-aminophenoxy)ethane-N, N, N′, N′-tetraacetic acid/AM (BAPTA/AM) did not prevent 2,5-dimethylphenol’s cytotoxicity. Together, in PC3 cells, 2,5-dimethylphenol induced [Ca2+]i rises that involved Ca2+?entry through PKC-regulated store-operated Ca2+?channels and PLC-dependent Ca2+?release from the endoplasmic reticulum. 2,5-Dimethylphenol induced cytotoxicity in a Ca2+-independent manner. 相似文献
5.
Chih‐Chuan Pan Chen‐Fu Shaw Jong‐Khing Huang Chun‐Chi Kuo Daih‐Huang Kuo Pochuen Shieh Ti Lu Wei‐Chuan Chen Chin‐Man Ho Chung‐Ren Jan 《Drug development research》2010,71(5):323-330
The effect of nortriptyline, a tricyclic antidepressant, on Ca2+ regulation and viability in human prostate cancer cells (PC3) is unclear. The present study examined whether nortriptyline altered basal [Ca2+]i levels in suspended PC3 cells using fura‐2 as a Ca2+‐sensitive fluorescent probe. Nortriptyline (50–500 µM) increased [Ca2+]i in a concentration‐dependent fashion. The Ca2+ signal was partially reduced by removing extracellular Ca2+, indicating that Ca2+ entry and release both contributed to the [Ca2+]i rise. Nortriptyline induced Mn2+ influx, leading to quench of fura‐2 fluorescence, suggesting Ca2+ influx. This Ca2+ influx was inhibited by activation of protein kinase C, but not by inhibition of L‐type Ca2+ channels. In Ca2+‐free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor, thapsigargin nearly abolished nortriptyline‐induced Ca2+ release. Conversely, pretreatment with nortriptyline greatly reduced the inhibitor‐induced [Ca2+]i rise, suggesting that nortriptyline released Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C did not change the nortriptyline‐induced [Ca2+]i rise. Nortriptyline at a concentration of 10 µM increased viability in a Ca2+‐independent manner. At 50 µM, nortriptyline killed 45% of cells. Nortriptyline at 10 µM did not induce apoptosis, but at 50 µM induced significant apoptosis measured by propidium iodide staining. Together, in PC3 cells, nortriptyline induced [Ca2+]i rises by causing the phospholipase C‐independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via the protein kinase C‐sensitive pathway. Nortriptyline also induced both cell proliferation and death in a concentration‐dependent manner. Apoptosis was involved in the cell death. Drug Dev Res 71:323–330, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
6.
+ 《Pharmacological research》2001,44(6):547
The effect of histamine on intracellular free Ca 2+levels ([Ca 2+] i) in PC3 human prostate cancer cells and the underlying mechanism were evaluated using fura-2 as a Ca 2+dye. Histamine at concentrations between 0.1 and 50 μM increased [Ca 2+] iin a concentration-dependent manner with an EC 50value of 1 μM. The [Ca 2+] iresponse comprised an initial rise and a slow decay, which returned to baseline within 3 min. Extracellular Ca 2+removal inhibited 50% of the [Ca 2+] isignal. In the absence of extracellular Ca 2+, after cells were treated with 1 μM thapsigargin (an endoplasmic reticulum Ca 2+pump inhibitor), 10 μM histamine did not increase [Ca 2+] i. After pretreatment with 10 μM histamine in a Ca 2+-free medium for several minutes, addition of 3 mM Ca 2+induced [Ca 2+] iincreases. Histamine (10 μM)-induced intracellular Ca 2+release was abolished by inhibiting phospholipase C with 2 μM 1-(6-((17 β-3- methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 10 μM pyrilamine but was not altered by 50 μM cimetidine. Collectively, the present study shows that histamine induced [Ca 2+] itransients in PC3 human prostate cancer cells by stimulating H1 histamine receptors leading to Ca 2+release from the endoplasmic reticulum in an inositol 1,4,5-trisphosphate-dependent manner, and by inducing Ca 2+entry. 相似文献
7.
《Drug and chemical toxicology》2013,36(4):456-462
Celecoxib has been shown to have an antitumor effect in previous studies, but the mechanisms are unclear. Ca2+ is a key second messenger in most cells. The effect of celecoxib on cytosolic free Ca2+ concentrations ([Ca2+]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 [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. Celecoxib-induced Ca2+ influx was not blocked by L-type Ca2+ entry inhibitors or protein kinase C/A modulators [phorbol 12-myristate 13-acetate (PMA), GF109203X, H-89], but was inhibited by the phospholipase A2 inhibitor, aristolochic acid. In Ca2+-free medium, 30 μM of celecoxib failed to induce a [Ca2+]i rise after pretreatment with thapsigargin (an endoplasmic reticulum [ER] Ca2+ pump inhibitor). Conversely, pretreatment with celecoxib inhibited thapsigargin-induced Ca2+ release. Inhibition of phospholipase C with U73122 did not change celecoxib-induced [Ca2+]i rises. Celecoxib induced slight cell death in a concentration-dependent manner, which was enhanced by chelating cytosolic Ca2+ with BAPTA. Collectively, in PC3 cells, celecoxib induced [Ca2+]i rises by causing phospholipase C–independent Ca2+ release from the ER and Ca2+ influx via non-L-type, phospholipase A2-regulated Ca2+ channels. These data may contribute to the understanding of the effect of celecoxib on prostate cancer cells. 相似文献
8.
Jue-Long Wang Chiang-Ting Chou Wei-Zhe Liang Cherng-Jer Wu Chun-Chi Kuo 《Toxicology mechanisms and methods》2019,29(2):138-145
Timolol is a medication used widely to treat glaucoma. Regarding Ca2+ signaling, timolol was shown to modulate Ca2+-related physiology in various cell types, however, the effect of timolol on Ca2+ homeostasis and cell viability has not been explored in human prostate cancer cells. The aim of this study was to explore the effect of timolol on intracellular Ca2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells. Timolol at concentrations of 100–1000?μM induced [Ca2+]i rises. The Ca2+ signal in Ca2+-containing medium was reduced by removal of extracellular Ca2+ by approximately 75%. Timolol (1000?μM) induced Mn2+ influx suggesting of Ca2+ entry. Timolol-induced Ca2+ entry was partially inhibited by three inhibitors of store-operated Ca2+ channels: nifedipine, econoazole and SKF96365, and by a protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate [PMA]) or an inhibitor (GF109203X). In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished timolol-evoked [Ca2+]i rises. Conversely, treatment with timolol abolished thapsigargin-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished timolol-induced [Ca2+]i rises. Timolol at concentrations between 200 and 600?μM killed cells in a concentration-dependent fashion. Chelation of cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not reverse cytotoxicity of timolol. Together, in PC3 cells, timolol induced [Ca2+]i rises by evoking Ca2+release from the endoplasmic reticulum in a PLC-dependent manner, and Ca2+ influx via PKC-regulated store-operated Ca2+ entry. Timolol also caused cell death that was not linked to preceding [Ca2+]i rises. 相似文献
9.
Daih‐Huang Kuo Li‐Min Liu Hsin‐Wei Chen Fu‐An Chen Chung‐Ren Jan 《Drug development research》2010,71(4):240-248
The effect of econazole on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability was explored in human oral cancer cells (OC2), using the fluorescent dyes fura‐2 and WST‐1, respectively. Econazole at concentrations of >1 µM increased [Ca2+]i in a concentration‐dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The econazole‐induced Ca2+ influx was sensitive to blockade of aristolochic acid (phospholipase A2 inhibitor) and GF109203X (PKC inhibitor). In Ca2+‐free medium, after treatment with 1 µM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 30 µM econazole failed to induce a [Ca2+]i rise. Inhibition of phospholipase C with 2 µM U73122 substantially suppressed econazole‐induced [Ca2+]i rise. At concentrations of 5–70 µM econazole killed cells in a concentration‐dependent manner. The cytotoxic effect of 50 µM econazole was enhanced by prechelating cytosolic Ca2+ with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA). The ERK MAPK inhibitor, PD98059 (10 µM), also enhanced 20 µM econazole‐induced cell death. Propidium iodide staining data suggest that econazole induced apoptosis between concentrations of 10–70 µM. Collectively, in OC2 cells, econazole induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from phospholipase A2/PKC‐regulated Ca2+ channels. Furthermore, econazole caused cell death appeared to be regulated by ERK MAPK. Drug Dev Res 71: 240–248, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
10.
异丙酚对PC12细胞膜流动性及[Ca~(2+)]_i的影响 总被引:4,自引:1,他引:3
目的 研究异丙酚对PC12细胞膜流动性及 [Ca2 + ]i的影响。方法 以PC12细胞作为神经细胞模型 ,加入不同浓度的异丙酚 ,用荧光偏振法测定细胞膜微粘度 η的动态变化 ,用激光扫描共聚焦显微镜检测 [Ca2 + ]i 随时间变化曲线。结果 ①异丙酚各剂量组的 η值均降低 ,并呈现剂量依赖性 ;② 30、10 0mg·L-1的异丙酚在加药后 2 0~ 30s使[Ca2 + ]i 短暂升高 ,[Ca2 + ]i的峰值分别比加药前增加了119%和 14 0 % ,但在 5 0s内均恢复到加药前水平。结论 异丙酚的全麻作用机制可能与细胞膜流动性增高有关 相似文献
11.
Ai-hui XU Zhi-min HU Jian-bo QU Shang-ming LIU Ali Kazim Abbas SYED Hui-qing YUAN Hong-xiang LOU 《Acta pharmacologica Sinica》2010,31(5):609-615
Aim:
To investigate the cytotoxic effects of four cyclic bisbibenzyls, Riccardin C (Ric), Pakyonol (Pak), Marchantin M (Mar), and Plagiochin E (Pla) against chemoresistant prostate cancer PC3 cells.Methods:
Cell growth was assayed by MTT method, and apoptotic related protein Bcl-2 and Bax, poly(ADP-ribose) polymerase (PARP) were examined by Western blotting. Cell cycle and apoptosis of PC3 cells were evaluated with flow cytometry and morphologic examinations.Results:
The four compounds inhibited proliferation and elicited cell death in a dose- and time-dependent manner with IC50 values of 3.22 μmol/L for Ric, 7.98 μmol/L for Pak, 5.45 μmol/L for Mar, and 5.99 μmol/L for Pla, respectively. Furthermore, exposed to these chemicals caused a decrease in the antiapoptotic protein Bcl-2 and an increase in proapoptotic Bax expression. PARP cleavage and caspase-3 activity were also observed.Conclusion:
The results suggest that cyclic bisbibenzyls could be used for the development of novel therapeutic chemicals against prostate cancer. 相似文献12.
Wei-Chuan ChenShu-Shong Hsu Chiang-Ting Chou Chun-Chi KuoJong-Khing Huang Yi-Chien FangHong-Tai Chang Jeng-Yu TsaiWei-Chuan Liao Being-Whey WangPochuen Shieh Daih-Huang KuoChung-Ren Jan 《Toxicology in vitro》2011,25(3):636-643
The effect of diallyl disulfide (DADS) on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells is unclear. This study explored whether DADS changed [Ca2+]i in PC3 cells by using fura-2. DADS at 50-1000 μM increased [Ca2+]i in a concentration-dependent manner. The signal was reduced by removing Ca2+. DADS-induced Ca2+ influx was not inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators; but was inhibited by aristolochic acid. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished DADS-induced [Ca2+]i rise. Incubation with DADS inhibited thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter DADS-induced [Ca2+]i rise. At 500-1000 μM, DADS killed cells in a concentration-dependent manner. The cytotoxic effect of DADS was partly reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). Propidium iodide staining suggests that DADS (500 μM) induced apoptosis in a Ca2+-independent manner. Annexin V/PI staining further shows that 10 μM and 500 μM DADS both evoked apoptosis. DADS also increased reactive oxygen species (ROS) production. Collectively, in PC3 cells, DADS induced [Ca2+]i rise probably by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-sensitive channels. DADS induced Ca2+-dependent cell death, ROS production, and Ca2+-independent apoptosis. 相似文献
13.
《Environmental toxicology and pharmacology》2015,39(3):800-806
Melamine is thought to be an endocrine disrupter that affects physiology in cells. This study examined the effect of melamine on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells. Melamine evoked [Ca2+]i rises concentration-dependently. Melamine-evoked Ca2+ entry was inhibited by nifedipine, econazole, SKF96365, GF109203X and phorbol 12-myristate 13 acetate. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited melamine-evoked [Ca2+]i rise. Conversely, treatment with melamine abolished thapsigargin-evoked [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter melamine-evoked [Ca2+]i rise. Melamine at 500–800 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in PC3 cells, melamine induced [Ca2+]i rises by evoking phospholipase C-independent Ca2+ release from the endoplasmic reticulum, and Ca2+ entry via protein kinase C-regulated store-operated Ca2+ entry. Melamine also caused Ca2+-independent cell death. 相似文献
14.
Literature has shown that diosgenin, a naturally occurring sapogenin, inducedcytotoxic effects in many cancer models. This study investigated the effect of diosgenin on intracellular Ca2+ concentration ([Ca2+]i) and cytotoxicity in PC3 human prostate cancer cells. Diosgenin (250‐1000 μM) caused [Ca2+]i rises which was reduced by Ca2+ removal. Treatment with thapsigargin eliminated diosgenin‐induced [Ca2+]i increases. In contrast, incubation with diosgeninabolished thapsigargin‐caused [Ca2+]i increases. Suppression of phospholipase C with U73122 eliminated diosgenin‐caused [Ca2+]i increases. Diosgenin evoked Mn2+ influx suggesting that diosgenin induced Ca2+ entry. Diosgenin‐induced Ca2+influx was suppressed by PMA, GF109203X, and nifedipine, econazole, or SKF96365. Diosgenin (250‐600 μM) concentration‐dependently decreased cell viability. However, diosgenin‐induced cytotoxicity was not reversed by chelation of cytosolic Ca2+ with BAPTA/AM. Together, diosgenin evoked [Ca2+]i increases via Ca2+ release and Ca2+ influx, and caused Ca2+‐non‐associated deathin PC3 cells. These findings reveal a newtherapeutic potential of diosgenin for human prostate cancer. 相似文献
15.
Tseng LL Huang CJ Hsu SS Chen JS Cheng HH Chang HT Jiann BP Jan CR 《Clinical and experimental pharmacology & physiology》2004,31(10):732-737
In human MG63 osteosarcoma cells, the effect of calmidazolium on [Ca(2+)](i) and proliferation was explored using fura-2 and ELISA, respectively. Calmidazolium, at concentrations greater than 0.1 micromol/L, caused a rapid increase in [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 0.5 micromol/L). The calmidazolium-induced [Ca(2+)](i) increase was reduced by 66% by removal of extracellular Ca(2+). In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic increase in [Ca(2+)](i), after which the effect of calmidazolium to increase [Ca(2+)](i) was completely inhibited. U73122, an inhibitor of phospholipase C (PLC), abolished histamine (but not calmidazolium)-induced increases in [Ca(2+)](i). Pretreatment with phorbol 12-myristate 13-acetate to activate protein kinase C inhibited the calmidazolium-induced increase in [Ca(2+)](i) in Ca(2+)-containing medium by 47%. Separately, it was found that overnight treatment with 2-10 micromol/L calmidazolium inhibited cell proliferation in a concentration-dependent manner. These results suggest that calmidazolium increases [Ca(2+)](i) by stimulating extracellular Ca(2+) influx and also by causing release of intracellular Ca(2+) from the endoplasmic reticulum in a PLC-independent manner. Calmidazolium may be cytotoxic to osteosarcoma cells. 相似文献
16.
Gwo-Ching Sun Wei-Zhe Liang Chung-Ren Jan 《Clinical and experimental pharmacology & physiology》2020,47(1):111-118
Glyburide is an agent commonly used to treat type 2 diabetes and also affects various physiological responses in different models. However, the effect of glyburide on Ca2+ movement and its related cytotoxicity in prostate cancer cells is unclear. This study examined whether glyburide altered Ca2+ signalling and viability in PC3 human prostate cancer cells and investigated those underlying mechanisms. Intracellular Ca2+ concentrations ([Ca2+]i) in suspended cells were measured by using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by WST-1 assay. Glyburide at concentrations of 100–1000 μM induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 60%. In Ca2+-containing medium, glyburide-induced Ca2+ entry was inhibited by 60% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA) and inhibitor (GF109203X), and modulators of store-operated Ca2+ channels (nifedipine, econazole and SKF96365). Furthermore, glyburide induced Mn2+ influx suggesting of Ca2+ entry. In Ca2+-free medium, inhibition of phospholipase C (PLC) with U73122 significantly inhibited glyburide-induced [Ca2+]i rises. Treatment with the endoplasmic reticulum (ER) Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished glyburide-evoked [Ca2+]i rises. Conversely, treatment with glyburide abolished BHQ-evoked [Ca2+]i rises. Glyburide at 100–500 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in PC3 cells, glyburide induced [Ca2+]i rises by Ca2+ entry via PKC-sensitive store-operated Ca2+ channels and Ca2+ release from the ER in a PLC-dependent manner. Glyburide also caused Ca2+-independent cell death. This study suggests that glyburide could serve as a potential agent for treatment of prostate cancer. 相似文献
17.
The sphingolipid metabolites sphingosine-1-phosphate (S1P) and sphingosylphosphorylcholine (SPC) can be involved in cellular growth and apoptosis, by both receptor-dependent and -independent mechanisms. We investigated the role of S1P and SPC in intracellular Ca2+ elevation, cell proliferation and cell death in DU 145 and PC3 hormone-refractory prostate cancer cell lines. S1P and SPC increased intracellular Ca2+ levels, most likely in a receptor-independent manner. Surprisingly, both S1P and SPC did not stimulate but rather reduced cell growth through induction of apoptosis. Therefore, antagonists targeted against S1P, SPC and their receptors do not appear to be promising new approaches in the treatment of hormone-refractory prostate cancer. 相似文献
18.
1. The effect of external ATP on the membrane current was investigated in PC12 cells by whole-cell voltage-clamp techniques. 2. Lower concentrations of ATP (1 or 10 mumol/L) induced only an inward current at 1 mmol/L EGTA in the K+ pipette solution, while higher concentrations of ATP (100 mumol/L and 1 mmol/L) induced an outward current following the inward current. 3. Lowering the EGTA concentration in the pipette solution induced a larger outward current following ATP application. The membrane potential at which the outward current crossed with the control before ATP application was more negative at lower concentrations of EGTA in the pipette. 4. The development of the outward current was blocked by a Ca(2+)-free external solution, 5 mmol/L tetraethylammonium and a Cs+ pipette solution instead of K+, indicating that the outward current was a Ca(2+)-activated K+ current. 5. Charybdotoxin (0.1 mumol/L) and iberiotoxin (0.1 mumol/L), but not apamin (0.2 mumol/L) blocked the development of the outward current, indicating the ATP-induced outward current is a BK-type Ca(2+)-activated K+ channel current and not the SK type. 6. UTP had no effect on the membrane current, indicating that the ATP-induced current change was not mediated by P2u but by P2x purinoceptor. 7. In conclusion, stimulation of P2x purinoceptors by ATP induces a Ca(2+)-permeable inward current that results in increases in intracellular Ca2+ concentrations and activation of a BK-type Ca(2+)-activated K+ current in PC12 cells. 相似文献
19.
Guo-hai SHI Ding-wei YE Xu-dong YAO Shi-ling ZHANG Bo DAI Hai-liang ZHANG Yi-jun SHEN Yao ZHU Yi-ping ZHU Wen-jun XIAO Chun-guang MA 《Acta pharmacologica Sinica》2010,31(7):867-873
Aim:
To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel.Methods:
A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3′UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot.Results:
A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established . Using microarrays, miR-21 was found to be up-regulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC50 values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells.Conclusion:
Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment. 相似文献20.
目的 体外研究褪黑素 (melatonin ,MLT)对人前列腺癌PC3细胞的增殖抑制作用及与 5 Fu联合用药的的影响。方法 用细胞计数法绘制细胞生长曲线、MTT比色法测定细胞活力、改良对硝基酚法测定酸性磷酸酶 (ACP)、改良二苯胺法测细胞内DNA含量及考马斯亮蓝法测定蛋白含量 ,并观察与 5 Fu联合用药对PC3细胞的影响。结果 MLT对PC3、CoLo2 0 5、K562和HeLa细胞的IC50 分别为 (1 2 0±0 30 )、(1 2 7± 0 1 2 )、(1 60± 0 1 6)和 (2 2 5± 0 1 1 )mmol·L- 1 ,MLT对上述细胞增殖的抑制呈时间和浓度依赖性 ,MLT减少PC3细胞的蛋白、DNA含量和降低酸性磷酸酶活性 ,MLT与 5 Fu 0 5mg·L- 1 联合用药有协同作用。结论 MLT对体外培养的肿瘤细胞的增殖有抑制作用 ,与 5 Fu联合用药有协同作用 相似文献