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1.
研究鸟氨酸脱羧酶抗酶蛋白对人红白血病K562细胞增殖、三氧化二砷( As2O3)诱导凋亡时的影响。方法: 定点突变技术构建缺失frameshift位点的pEGFP-N1-AZ1-mutation重组表达载体。脂质体法转染K562细胞,通过G418筛选获得稳定表达antizyme1的K562pAZ1m细胞系。采用不同浓度的As2O3处理细胞,通过MTT法检测细胞增殖,流式细胞术分析细胞周期及凋亡变化。并通过RT-PCR方法检测antiyme1转染对cyclin D1和survivin基因表达的影响。结果:获得稳定表达antizyme1的K562-AZ1m细胞株后,其增殖能力明显减慢。CyclinD1基因表达降低,细胞主要停滞于G0/G1期。在 As2O3的诱导作用下,细胞凋亡增多,survivin基因表达降低。结论:AZ1基因能够抑制K562细胞增殖,通过对cyclinD1的负调控使细胞周期停滞于G0/G1期。并可能通过下调survivin表达来加强 As2O3对其的诱导凋亡作用 相似文献
2.
Shih-Chung Wang Mei-Chin Lu Hsiu-Lin Chen Hsing-I Tseng Yu-Yuan Ke Yang-Chang Wu Pei-Yu Yang 《Cell biology international》2009,33(12):1230-1236
Calotropin is one of cardenolides isolated from milkweed used for medicinal purposes in many Asian countries. Whereas calotropin possesses cytotoxicity against several cancer cells, the mechanisms of action remain unclear. We set out to evaluate the cytotoxic mechanism of calotropin on human chronic myeloid leukemia K562 cells. Calotropin inhibited the growth of K562 cells in a time- and dose-dependent manner by G2/M phase arrest. It upregulated the expression of p27 leading to this arrest by downregulating the G2/M regulatory proteins, cyclins A and B, and by upregulating the cdk inhibitor, p27. Furthermore, it downregulated anti-apoptotic signaling (XIAP and survivin) and survival pathways (p-Akt and NFκB), leading to caspase-3 activation which resulted in the induction of apoptosis. In all, calotropin exerted its anticancer activity on K562 cells by modulating the pro-survival signaling that leads to induction of apoptosis. 相似文献
3.
In this study, we extracted a polysaccharide (short-chain polysaccharide [PS]) from porcine cartilage and examined its function
in chronic myeloid leukaemia by using human K562 cells and mouse L1210 cells. Results of cell proliferation assay indicated
that PS inhibited cancer cell growth at different concentrations, while it had little effect on normal cells. The presence
of morphological aspects of apoptosis, such as nuclear shrinkage, was shown in H&E stained sections. The occurrence of PS-induced
apoptosis was confirmed by TUNEL assay and cell cycle analysis. The results of immunofluorescent staining indicated the molecular
mechanism underlying. Through interfering with the cell cycle of tumor cells, PS may induce apoptosis by downregulating the
expression level of cyclin D1 and upregulating the level of p21 protein. Correlation analysis of apoptosis and MAPK suggested
that inactivation of ERK was crucial for PS induced apoptosis, while JNK phosphorylation had a small effect and p38 was not
involved. In vivo assay showed that PS inhibited L1210 cell growth in vivo and prolonged the life span of L1210-bearing mice. We conclude that PS is a polysaccharide with anticancer effects and induced
apoptosis in human K562 cells. 相似文献
4.
Banfalvi G Klaisz M Ujvarosi K Trencsenyi G Rozsa D Nagy G 《Apoptosis : an international journal on programmed cell death》2007,12(12):2271-2283
Exponentially growing human erythroleukemia K562 cells were synchronized by centrifugal elutriation prior to and after Co60 γ-irradiation (4 Gy). Forward scatter flow cytometry used for size analysis revealed the increase of an early apoptotic cell
population ranging from lower (0.05 C-value) to higher DNA content (∼1 C) as the cells progressed through the S phase. The
increase in cellular DNA content expressed in C-values correlated with apoptotic chromatin changes manifested as many small
apoptotic bodies in early S phase and larger but less numerous disintegrated apoptotic bodies in late S phase. Most significant
changes after exposure to γ-irradiation took place in early S phase resulting in an increase of nuclear size by more than
50%. Cell fractions containing irradiated cells showed enhanced growth arrest at 2.4 C-value, which was accompanied by apoptosis.
Apoptotic cell cycle arrest near to the G1/G0 checkpoint and apoptotic changes indicate that the radiation resistance of K562 cells is related to the bypass of the early
stage of the p53 apoptotic pathway. Apoptotic changes in chromatin structure induced by γ-irradiation indicate that these
injury-specific changes can be identified and distinguished from chromatin changes induced by UV radiation or heavy metals. 相似文献
5.
A series of substituted urea derivatives, compounds 1-14, were synthesized and evaluated for their cytotoxic activities against the human-leukemia K562 cell line. Two structurally simple compounds, 7 and 12, both incorporating a morpholine ring, were found to be highly active, with IC50 values of ca. 0.25 microM. 相似文献
6.
Sun Jeong Jang Heung Woo Choi Doo Li Choi Sehyeon Cho Hong-Kun Rim Hye-Eun Choi Ki-Sun Kim Minghua Huang Hyewhon Rhim Kyung-Tae Lee Jae Yeol Lee 《Bioorganic & medicinal chemistry letters》2013,23(24):6656-6662
The growth inhibition of human cancer cells via T-type Ca2+ channel blockade has been well known. Herein, a series of new 3,4-dihydroquinazoline derivatives were synthesized via a brief SAR study on KYS05090 template and evaluated for both T-type Ca2+ channel (Cav3.1) blockade and cytotoxicity on three human ovarian cancer cells (SK-OV-3, A2780 and A2780-T). Most of compounds except 6i generally exhibited more potent cytotoxicity on SK-OV-3 than mibefradil as a positive control regardless of the degree of T-type channel blockade. In particular, eight compounds (KYS05090, 6a and 6c–6h) showing strong channel blockade exhibited almost equal and more potent cytotoxicity on A2780 when compared to mibefradil. On A2780-T paclitaxel-resistant human ovarian carcinoma, two compounds (KYS05090 and 6d) were 20-fold more active than mibefradil. With respect to cell cycle arrest effect on A2780 and A2780-T cells, KYS05090 induced large proportion of sub-G1 phase in the cell cycle progression of A2780 and A2780-T, meaning the induction of cancer cell death instead of cell cycle arrest via blocking T-type Ca2+ channel. Among new analogues, compounds 6g and 6h induced cell cycle arrest at G1 phase of A2780 and A2780-T cells in dose-dependent manner and exhibited strong anti-proliferation effects of ovarian cancer cells by blocking T-type Ca2+ channel. Furthermore, 6g and 6h possessing strong cytotoxic effects could induce apoptosis of A2780 cells, which was detected by confocal micrographs using DAPI staining. 相似文献
7.
BackgroundCoumarins occurs naturally across plant kingdoms exhibits significant pharmacological properties and pharmacokinetic activity. The conventional, therapeutic agents are often associated with poor stability, absorption and increased side effects. Therefore, identification of a drug that has little or no-side effect on humans is consequential. Here, we investigated the antiproliferative activity of styrene substituted biscoumarin against various human breast cancer cell lines, such as MCF-7, (ER-) MDA-MB-231 and (AR+) MDA-MB-453. Styrene substituted biscoumarin induced cell death by apoptosis in MDA-MB-231 cell line was analyzed.MethodsAntiproliferative activity of Styrene substituted biscoumarin was performed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Styrene substituted biscoumarin induced apoptosis was assessed by Hoechst staining, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining and flow cytometric analysis. Migratory and proliferating characteristic of breast cancer cell line MDA-MB-231 was also analyzed by wound healing and colony formation assay. Furthermore, mRNA expression of BAX and BCL-2 were quantified using qRT-PCR and protein expression level analyzed by Western blot.ResultsThe inhibition concentration (IC50) of styrene substituted biscoumarin was assayed against three breast cancer cell lines. The inhibition concentration (IC50) value of styrene substituted biscoumarin toward MDA-MB-231, MDA-MB-453 and MCF-7 cell lines was 5.63, 7.30 and 10.84 μg/ml respectively. Styrene substituted biscoumarin induced apoptosis was detected by Hoechst staining, DAPI/PI analysis and flow-cytometric analysis. The migration and proliferative efficiency of MDA-MB-231 cells were completely arrested upon styrene substituted biscoumarin treatment. Also, mRNA gene expression and protein expression of pro-apoptotic (BAX) and anti-apoptotic (BCL-2) genes were analyzed by qRT-PCR and western blot analysis upon styrene substituted biscoumarin treatment to MDA-MB-231 cells. Our results showed that styrene substituted biscoumarin downregulated BCL-2 gene expression and upregulated BAX gene expression to trigger apoptotic process.ConclusionStyrene substituted biscoumarin could induce apoptosis through intrinsic mitochondrial pathway in breast cancer cell lines, particularly in MDA-MB-231. Our data suggest that styrene substituted biscoumarin may act as a potential chemotherapeutic agent against breast cancer. 相似文献
8.
目的:探讨萝卜硫素靶向RASD1,对宫颈癌细胞(HELA)凋亡及周期的影响机制。方法:不同浓度的萝卜硫素(SFN)作用于HELA细胞48h,采用CCK-8法检测SFN对HELA细胞增殖的影响;采用RT-PCR法检测SFN对RASD1基因mRNA表达水平的影响;采用Western印迹法检测SFN对RASD1蛋白表达水平的影响;采用流式细胞技术检测加药以及过表达RASD1对HELA细胞凋亡及周期的影响,采用Western blot检测HELA中cleaved-caspase3和cleaved-parp相关凋亡蛋白以及p21和cdc2周期相关蛋白的影响。结果:SFN抑制宫颈癌细胞增殖,且加药组中RASD1的mRNA和蛋白表达水平明显高于对照组,差异有统计学意义(P0.05)。流式细胞凋亡分析结果提示:加SFN或是过表达RASD1细胞组凋亡率明显高于对照组,Western blot结果表明加SFN或过表达RASD1后细胞cleaved-caspase3以及cleaved-parp蛋白水平升高,差异具有统计学意义(P0.05);ModFit LT软件分析结果表明加SFN或过表达RASD1细胞S期显著低于对照组,G2/M期细胞增多,同时Western blot结果示p21蛋白的表达水平增高,而cdc2蛋白表达降低,其差异有统计学意义(P0.05)。结论:在宫颈癌HELA细胞中RASD1作为SFN的作用靶点,诱导细胞凋亡和细胞周期阻滞。 相似文献
9.
Wesierska-Gadek J Schreiner T Maurer M Waringer A Ranftler C 《Cellular & molecular biology letters》2007,12(2):280-293
Estrogens play an important role in the growth and terminal differentiation of the mammary gland. Prolonged exposure to estrogens
seems to predispose women to breast cancer. It recently became evident that not only the intrinsic hormonal status but also
external factors such as the occurrence of pharmaceuticals and chemicals with hormone activity in the environment may put
women at greater risk of developing breast cancer. We focused on the interference of endocrine disruptors in breast cancer
therapy. We observed that phenol red added to the culture medium strongly promoted the cell proliferation and cell cycle progression
of human cells expressing the estrogen receptor, and affected their susceptibility to chemotherapy. 相似文献
10.
Yiting Wang Yanmei Chen Xiaoling Cheng Ke Zhang Hangyu Wang Bo Liu Jinhui Wang 《Bioorganic & medicinal chemistry》2018,26(12):3491-3501
Cyclin-dependent kinase 2 (CDK2) plays a key role in eukaryotic cell cycle progression which could facilitate the transition from G1 to S phase. The dysregulation of CDK2 is closely related to many cancers. CDK2 is utilized as one of the most studied kinase targets in oncology. In this article, 24 benzamide derivatives were designed, synthesized and investigated for the inhibition activity against CDK2. Our results revealed that the compound 25 is a potent CDK2 inhibitor exhibiting a broad spectrum anti-proliferative activity against several human breast cancer cells. Additionally, compound 25 could block cell cycle at G0 or G1 and induce significant apoptosis in MDA-MB-468 cells. These findings highlight a rationale for further development of CDK2 inhibitors to treat human breast cancer. 相似文献
11.
The photodynamic response of the anthraquinone anticancer drug aclarubicin (ACL) was investigated in vitro and compared with that of mitoxantrone (MTX). Cultured immortalized rodent B14 and NIH 3T3 cells were used in the experiments as a model for cells with neoplastic phenotype. Long-term cytotoxicity and inhibition of cell proliferation assayed by the clonal growth and MTT-tetrazolium methods were estimated to compare the efficacy of aclarubicin and mitoxantrone in photosensitizing cells and their death after non-thermal exposure to monochromatic laser light. Green He-Ne (543.5 nm) or red semiconductor (670 nm) low-power laser (LPL) irradiations were applied. Different dose-responses of both cell lines to aclarubicin and mitoxantrone were found so that the cytotoxicity of MTX was considerably greater than the cytotoxicity of ACL. Phototherapy response (P < 0.0001) was observed only for B14 cells after sensitisation with aclarubicin. Under the same conditions no significant effect of red light irradiation (semiconductor 670 nm laser) on survival of both cell lines treated with mitoxantrone was found. 相似文献
12.
Malti Arya Nidhi Mishra Pooja Singh Chandra B. Tripathi Poonam Parashar Mahendra Singh Krishna P. Gupta Shubhini A. Saraf 《Journal of cellular physiology》2019,234(9):15527-15536
Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer. 相似文献
13.
Carvacrol (CVC) is a phenolic monoterpene present in many essential oils of medicinal and aromatic plants and has attracted attention because of its beneficial biological activities. To date, although various biological activities of CVC have been demonstrated, its neurotoxicity on cultured primary rat neurons and N2a neuroblastoma cells has never been explored. Therefore, in this present study, we aimed to describe in vitro antiproliferative and/or cytotoxic properties (by 3-(4,5 dimetylthiazol -2-yl)-2,5 diphenlytetrazolium bromide (MTT) test), genotoxic damage potentials (by single cell gel electrophoresis (SCGE) or Comet assay) and antioxidant activities (by total antioxidant capacity (TAC) and total oxidative stress (TOS) analysis) of CVC in vitro. Dose (0–400 mg/L) dependent effects of CVC were tested on both cultured primary rat neurons and N2a neuroblastoma cells. Statistical analysis of MTT assay results indicated significant (p < 0.05) decreases of cell proliferation rates in both cell types treated with CVC at 200 and 400 mg/L. On the other hand, the mean values of the total scores of cells showing DNA damage (for comet assay) was not found significantly different from the control values for both cells (p > 0.05). In addition, our results indicated that 10, 25 and 50 mg/L of CVC treatment caused increases of TAC levels in cultured primary rat neurons but not in the N2a cell line. However, CVC treatments led to increases of TOS levels in cultured primary rat neurons at only 400 mg/L while they led to increases of TOS levels in N2a neuroblastoma cells at 200 and 400 mg/L. The present findings demonstrated that CVC could be a source of antioxidant and chemopreventive activities to be studied on cancer diseases. 相似文献
14.
15.
《Saudi Journal of Biological Sciences》2023,30(2):103551
Bombyx mori silk sericin is a globular-like protein that is used as an antioxidant, antibacterial, and antitumor agent. In this current research, we isolated sericin by degumming process and formation of sericin-AgNO3 NPs confirmed by UV–vis spectra, SEM, EDX, FTIR, and XRD patterns. The sericin and sericin-AgNO3 NPs mediated changes in human breast cancer cells were determined. The antiproliferative activity of sericin-AgNO3 NPs was analyzed by MTT dye reduction assay. Alterations at molecular levels were investigated by qRT-PCR, while apoptotic effects were studied by nuclear DNA staining. After 72 h treatment, sericin and sericin-AgNO3 NPs showed significant antiproliferative effects in MDA-MB-231 (26 %) and MCF-7 (41 %) cells. Expression modification showed prominent stimulation of cell cycle arrest and stress related genes such as cyclin-dependent kinase inhibitors (CDKN1A, CDKN1B), and GADD family genes. RT-PCR results of the GADD family include GADD45A, B, G, 34, 153 and cyclin-dependent kinase inhibitors (CDKN1A, 1B) showed pronounced induction of 3.1 to 19.8-folds in MCF-7 cell line while induction in MDA-MB-231 cell line was 2.5 to 34.3-folds. Nuclear DAPI staining showed significant induction of apoptosis and nuclear fragmentation in MDA-MB-231 cells at a concentration of 1 mg/mL for both sericin and sericin-AgNO3 NPs. Meanwhile, in case of MCF-7 cells, after treatment with sericin and sericin-AgNO3 NPs (1 mg/mL), the cells changed into a round shape and lost their original spindle outlook in dose-dependent manners. We concluded that sericin-AgNO3 NPs have significant antiproliferative, apoptosis, and genetic profiling effects in both breast cancer cell lines at the highest concentration. 相似文献
16.
Ujvarosi K Hunyadi J Nagy G Pocsi I Banfalvi G 《Apoptosis : an international journal on programmed cell death》2007,12(11):2089-2099
Exponentially growing human erythroleukemia K562 cells were permeabilized and the dose dependent decrease of DNA synthesis rate was measured after ultraviolet (UV B, 290 nm) irradiation. Cells were able to overcome 2 and 5 J/m2 UV doses, partial recovery was observed at 15 J/m2, while at high (25 J/m2) UV dose replicative DNA synthesis remained suppressed. K562 cells were subjected to synchronization prior to and after UV irradiation (24 J/m2) and 18 fractions were collected by centrifugal elutriation. Cell cycle analysis by flow cytometry did not show early apoptotic cells after UV irradiation. The gradual increase in DNA content typical for non-irradiated cells was contrasted by an early S phase block between 2.2 and 2.4 C-values after UV irradiation. Cell cycle dependent chromatin changes after ultraviolet irradiation were seen as a fine fibrillary network covering the mainly fibrous chromatin structures and incompletely folded primitive chromosomes. Based on observations after UV irradiation and on earlier results with cadmium treatment and gamma irradiation, we confirm that typical chromatin changes characteristic to genotoxic agents can be recognized and classified. 相似文献
17.
Pro-apoptotic effect and cytotoxicity of genistein and genistin in human ovarian cancer SK-OV-3 cells 总被引:3,自引:0,他引:3
We investigated the effects of genistein and genistin on proliferation and apoptosis of human ovarian SK-OV-3 cells and explored the mechanism for these effects. SK-OV-3 cells were treated with genistein and genistin at various concentrations (ranging from 1 to 100 muM) either alone or in combination for 24 and 48 h. Cell proliferation was estimated using an MTT assay, and cell cycle arrest was evaluated using FACS. Caspase-3 activity and annexin-based cell cycle analysis were used as measures of apoptosis. In addition, genistein- and genistin-induced cytotoxicity was determined by measuring release of LDH. Genistein treatment for 24 or 48 h substantially inhibited SK-OV-3 cell proliferation in a dose-dependent manner, and genistin treatment for 48 h also inhibited cell proliferation. Genistein caused cell cycle arrest at G2/M phase in dose- and time-dependent manner, and genistin caused cell cycle arrest not only at G2/M phase but also at G1 phase. Genistein markedly induced apoptosis and significantly increased LDH release, whereas genistin did not affect LDH release. Moreover, exposure to both genistein and genistin in combination for 48 h induced apoptosis without increasing LDH release. Genistein and genistin inhibit cell proliferation by disrupting the cell cycle, which is strongly associated with the arrest induction of either G1 or G2/M phase and may induce apoptosis. Based on our findings, we speculate that both genistein and genistin may prove useful as anticancer drugs and that the combination of genistein and genistin may have further anticancer activity. 相似文献
18.
Inhibitory effect of phycocyanin from Spirulina platensis on the growth of human leukemia K562 cells
Yufeng Liu Lizhi Xu Ni Cheng Lijun Lin Chengwu Zhang 《Journal of applied phycology》2000,12(2):125-130
The effect of phycocyanin from Spirulinaplatensis on the growth of human chronic myelogenousleukemia-blast crisis K562 cells was studied bysemi-solid agar assay and cell viability measurement. Phycocyanin significantly inhibited the growth of K562cells in a dose-dependent manner. The IC50 value ofthe phycocyanin was 72.5 mg L-1. After the K562cells were cultured with phycocyanin for 6 days, flowcytometric assays showed that more K562 cells wereblocked to progress through S-phase and arrested at G1phase. DNA fragmentation assay indicated that therewas no ladder of DNA fragments of approximately 200-bpmultiples, indicating that apoptosis had not occurred. Western blot analysis showed that Bcl-2 protein wasexpressed, but its level remained unchanged, whereasthe expression level of c-myc increased. Thesefindings suggest that phycocyanin may be able toinhibit the growth of K562 cells by pathways otherthan apoptosis, and that changed a expression patternof the c-myc protein may be involved in such inhibition. 相似文献
19.
Haiyuan Zhang Ronald Thomas David Oupicky Fangyu Peng 《Journal of biological inorganic chemistry》2008,13(1):47-55
Two new copper thiosemicarbazone complexes with an ONNS quadridentate system were synthesized and evaluated for anticancer
activity on cisplatin-resistant neuroblastoma cells. Among these two copper complexes, the substituted 8-hydroxyquinoline-2-carboxaldehyde–4,4-dimethyl-3-thiosemicarbazide
(CuHQDMTS) exhibited stronger cell growth inhibition activity than the unsubstituted copper 8-hydroxyquinoline-2-carboxaldehyde
thiosemicarbazide complex (CuHQTS). Both CuHQTS and CuHQDMTS showed dose-dependent cell growth inhibition, cell cycle arrest
and apoptosis induction activities on the SK-N-DZ neuroblastoma cells. Increased expression of p53 protein molecules was detected
in the SK-N-DZ cells treated with CuHQTS. The data obtained in this study suggest that CuHQDMTS and CuHQTS hold potential
as new, effective drugs for treatment of refractory neuroblastoma in children. 相似文献
20.
The effect of specific caspase inhibitors on TNF-alpha and butyrate-induced apoptosis of intestinal epithelial cells 总被引:6,自引:0,他引:6
Tumour necrosis factor-alpha (TNF-alpha)-induced intestinal epithelial cell apoptosis may contribute to mucosal injury in inflammatory bowel disease. Inhibition of TNF-alpha-induced apoptosis, using specific caspase inhibitors could, therefore, be of benefit in the treatment of disease. In vitro, CaCo-2 colonic epithelial cells are refractory to apoptosis induced by TNF-alpha alone; however, TNF-alpha can act synergistically with the short-chain fatty acid (SCFA) and colonic fermentation product, butyrate, to promote apoptosis. TNF-alpha/butyrate-induced apoptosis was characterised by nuclear condensation and fragmentation and caspase-3 activation. Inhibitors of caspase-8 (z-IETD.fmk) and caspase-10 (z-AEVD.fmk) significantly reduced TNF-alpha/butyrate-induced apoptosis, based on nuclear morphology and terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labelling (TUNEL), although caspase inhibition was associated with a significant increase in cells demonstrating atypical nuclear condensation. Inclusion of atypical cells in calculations of total cell death, still demonstrated that z-IETD.fmk and z-AEVD.fmk (in combination) significantly reduced cell death. Reduction in cell death was associated with maintenance of viable cell number. Transmembrane resistance was also used a measure of the ability of caspase inhibitors to prevent TNF-alpha/butyrate-mediated damage to epithelial monolayers. TNF-alpha/butyrate resulted in a significant fall in transmembrane resistance, which was prevented by pre-treatment with z-IETD.fmk, but not z-AEVD.fmk. In conclusion, synthetic caspase inhibitors can reduce the apoptotic response of CaCo-2 colonic epithelial cells to TNF-alpha/butyrate, improve the maintenance of viable cell numbers and block loss of transmembrane resistance. We hypothesise that caspase inhibition could be a useful therapeutic goal in the treatment of inflammatory bowel conditions, such as ulcerative colitis. 相似文献