Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homoharringtonine (HHT) is a plant alkaloid with antileukemia activity that is currently being used for treatment of acute, chronic leukemias and MDS. In this study, we show that HHT can induce apoptosis in a variety of human myeloid leukemia cell lines (U937, HL-60, HEL, THP, and K562). U937 and HL60 cells undergo rapid apoptosis on treatment with HHT, as indicated by increased annexin V binding capacity, caspase-3 activation, and cleavage of poly(ADP-ribose) polymerase (PARP). In addition, the expression of bax is upregulated during HHT-induced cell death, whereas the expression of bcl-2 is only slightly decreased. Importantly, treatment of primary leukemic cells, obtained from acute myeloid leukemia patients, resulted in rapid apoptosis. Thus, our data provide the mechanism of HHT and justify the use of HHT in the treatment of human myeloid leukemia.
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PMID:Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP). 1522 52

To investigate the apoptotic effect of triptolide on MDS cell line MUTZ-1 cells and its mechanism, MUTZ-1 cells were incubated with indicated concentrations of triptolide. The growth of MUTZ-1 cells was observed by MTT assay and apoptosis was detected by DNA fragmentation analysis and flow cytometry using Annexin V-FITC/PI staining. The gene and protein expressions were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. The results showed that MUTZ-1 cell viability in presence of triptolide decreased markedly in a dose- and time-dependent manner. The growth-inhibitory IC50 value for triptolide treatment was 55.06 ng/ml. A DNA ladder pattern of internucleosomal fragmentation was observed. The translocation of phosphatidylserine at the outer surface of the cell plasma membrane could be induced by triptolide and its level increased following the augmentation of the drug concentration. Treatment of MUTZ-1 cells with triptolide for 12 hours resulted in the activation of caspase-3, cleavage of PARP and decrease of c-IAP2 mRNA. The expressions of pro-caspase 3 and c-IAP2 were inversely correlated with the incidence of apoptosis. (r = -0.907, P = 0.000; r = -0.919, P = 0.000 respectively). In conclusion, Triptolide inhibits MUTZ-1 cell growth by inducing apoptosis. The apoptotic effect of triptolide in MUTZ-1 cells is mediated by the caspase-3 activation and PARP cleavage. Moreover, the activation of caspase-3 may be associated with the down-regulation of c-IAP2.
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PMID:[Study of triptolide-induced apoptosis in MUTZ-1 cells and its allied mechanism]. 1597 36

To study the effects and possible mechanism of Vitamin K(2) (VK(2)) in the treatment of MDS-JSN04 cells, the changes of morphologic features of MDS-JSN04 cells were investigated by cytomorphology, the apoptosis of MDS-JSN04 cells was observed by transmission electron microscope; cellular proliferation was determined by the MTT assay; cell apoptosis, cell cycle shift and expression of myeloid-specific differentiation antigen (CD11b, CD13) were analyzed by flow cytometry (FCM). The expression of apoptosis-related genes bcl-2, survivin and bax were detected by retrotranscriptase polymerase chain reaction (RT-PCR); the activity of caspase-3 was determined by chemiluminescence assay. The results showed that the typical apoptotic morphological features appeared in cells treated with VK(2) for 72 hours; VK(2) induced apoptosis of MDS-JSN04 cells and in a dose-and-time-dependent manner, G(0)/G(1) cell arrest and significantly down-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax; the activity of caspase-3 significantly increased. It is concluded that VK(2) induces apoptosis of MDS-JSN04 cells through activating caspase-3 pathways and the apoptosis-related genes bcl-2, survivin may play an important role in this process.
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PMID:[Inhibition effect of vitamin K2 on human MDS-JSN04 cell line and its possible mechanism]. 1640 73

Vitamin K2 [menaquinone-4 (MK-4)] has been reported to induce apoptosis in hepatocellular carcinoma, leukemia, and MDS cell lines. The effects of MK-4 on the development of arthritis have never been addressed so far. In this study, we investigated the effect of MK-4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen-induced arthritis (CIA). We analyzed the effect of MK-4 on the proliferation of fibroblast-like synoviocytes (FLSs) using the 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The proapoptotic effect of MK-4 upon FLS was investigated with annexin V staining and DNA fragmentation and caspase 3/7 assays. Moreover, we analyzed the effect of MK-4 on the development of CIA in female dark agouti rats. Our results indicated that MK-4 inhibited the proliferation of FLS and the development of CIA in a dose-dependent manner. We concluded that MK-4 may represent a new agent for the treatment of RA in the setting of combination therapy with other disease-modifying antirheumatic drugs.
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PMID:Vitamin K and rheumatoid arthritis. 1848 89

SPAG6, which is a novel cancer-testis antigen, is overexpressed in myeloid malignancies. Previously, SPAG6 was found in UPD (uniparental disomy) region of myeloid cell DNA from MDS patients and reported that SPAG6 may be a predictive marker of minimal residual disease in pediatric acute myeloid, but the biological role of SPAG6 in myeloid malignancies remains unclear. The present study was undertaken to determine the expression and functional significance of SPAG6 in malignant myeloid hematologic cell lines. A short hairpin RNA (shRNA) targeting SPAG6 was designed that could specifically inhibit SPAG6 expression at the mRNA and protein levels when introduced into the malignant myeloid hematologic cell lines SKM-1 and K562. The results from flow cytometry and CCK-8 assays showed that SPAG6 silencing inhibited the proliferation of SKM-1/K562 by inducing apoptosis. Furthermore, SPAG6 silencing resulted in activation of caspase-3, -9 and -8 and upregulated the mRNA and protein expression of p53 and PTEN. Then, we subcutaneously inoculated the monoclonal cells into NOD/SCID mice to establish xenograft models, and we found that the SPAG6-shRNA lentivirus dramatically inhibited tumor growth and increased apoptosis in vivo. These findings demonstrate that SPAG6 might have a role in malignant myeloid hematologic cell proliferation and apoptosis by regulating caspase proteins and p53, suggesting that SPAG6 may be a potential therapeutic target.
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PMID:SPAG6 silencing inhibits the growth of the malignant myeloid cell lines SKM-1 and K562 via activating p53 and caspase activation-dependent apoptosis. 2540 88

Chidamide as a newly designed and synthesized histone deacetylase inhibitor induces an antitumor effect in various cancer, and it has been used in several clinical trials such as peripheral T cell lymphoma (PTCL). Here we demonstrate that Chidamide was able to increase the acetylation levels of histone H3 and decrease HDAC activity in MDS cell lines(SKM-1,MUTZ-1)and AML cell line(KG-1). In vitro, at low concentration (<250nM) of Chidamide inhibited cell proliferation and delayed G0/G1 cell cycle progression by down-regulating CDK2 and regulating p-P53 and P21 protein expression. Meanwhile,it also induced cell apoptosis by down-regulating Bcl-2 and up-regulating cleaved Caspase-3 and Bax protein expression.The results of the present study demonstrates the potential utility of Chidamide for the treatment of Myelodysplastic syndromes.
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PMID:A novel histone deacetylase inhibitor Chidamide induces G0/G1 arrest and apoptosis in myelodysplastic syndromes. 2754 Oct 47