Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeic acid phenethyl ester (CAPE) is one of the most effective components of propolis which is collected by honey bees. The aim of this study was to investigate the cytotoxic and apoptotic effects of CAPE in the CCRF-CEM cell line and to clarify the role of serine/threonine protein phosphatase 2A (PP2A) and human telomerase reverse transcriptase (hTERT) activity as an underlining mechanism of CAPE-induced apoptosis. Trypan blue dye exclusion test and XTT methods were used to evaluate the cytotoxicity and ELISA based oligonucleotide detection, which can be seen during apoptosis, was used to determine apoptosis. Acridine orange/ethidium bromide dye technique was also used to evaluate apoptosis. The cytotoxic effect of CAPE was detected in a dose and time dependent manner with the IC(50) of 1 muM. ELISA and acridine orange/ethidium bromide methods have shown remarkable apoptosis at 48th hour in CAPE treated cells. To investigate the role of PP2A in CAPE-induced apoptosis of CCRF-CEM cells, we performed combination studies with CAPE and, Calyculin A and Okadaic acid, which are very well known inhibitors of PP2A, in IC(20) of inhibitors and IC(50) of CAPE. Combination studies revealed synergistic effect of both drugs by concomitant use. Western blot analyses of PP2A catalytic and regulatory subunits showed down-regulation of expression of PP2A catalytic subunit in CAPE treated cells at 48th hour. Since, PP2A is important in hTERT (telomerase catalytic subunit) activation and deactivation, we also performed hTERT activity in CAPE treated cells simultaneously. Treating cells with IC(50) of CAPE for 96 h with the intervals of 24 h showed marked reduction of hTERT activity. The reduction of hTERT activity in CAPE treated CCRF-CEM cells was more prominent in the initial 48 h. The variation of hTERT activity in CAPE treated CCRF-CEM cells may be the reason for the protein phosphatase interaction that occurred after treatment with CAPE.
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PMID:Protein phosphatase 2A (PP2A) has a potential role in CAPE-induced apoptosis of CCRF-CEM cells via effecting human telomerase reverse transcriptase activity. 1785 32

Combination therapy could be of use for the treatment of fungal infections, especially those caused by drug-resistant fungi. However, the methods and approaches used for data generation and result interpretation need further optimizing. The fractional inhibitory concentration index (FICI) is the most commonly used method, but it has several drawbacks in characterizing antifungal drug interaction. Alternatively, some new methods can be used such as the DeltaE model (difference between the predicted and measured fungal growth percentages) and the response surface approach, which uses the concentration-effect relationship over the whole concentration range instead of just the MIC. In the present study, in vitro interactions between tacrolimus (FK506) and three azoles-fluconazole (FLC), itraconazole (ITR), and voriconazole (VRC)-against Candida albicans were evaluated by the checkerboard microdilution method and time-killing test. The intensity of the interactions was determined by visual reading and the spectrophotometric method in a checkerboard assay, and the nature of the interactions was assessed by nonparametric models of FICI and DeltaE. Colony counting and colorimetric viable detection methods (2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium hydroxide} [XTT] reduction test) were used for evaluating the combination antifungal effects over time. Synergistic and indifferent effects were found for the combination of FK506 and azoles against azole-sensitive strains, while strong synergy was found against azole-resistant strains analyzed by FICI. The DeltaE model gave more consistent results with FICI. The positive interactions were also confirmed by the time-killing test. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and azoles to augment activity against resistant C. albicans.
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PMID:In vitro interactions between tacrolimus and azoles against Candida albicans determined by different methods. 1805 77

Paclitaxel and docetaxel (taxoids) are chemotherapy agents whose mode of action is through an effect on cellular microtubules. Several studies have investigated their potential in the treatment of myeloid malignancies. The aim of our study was to investigate the potential role of the serine/threonine protein phosphatase system in docetaxel/paclitaxel induced cytotoxicity on HL 60 cells. The IC50 dose of paclitaxel and docetaxel were found as 20 and 5 nM respectively using trypan blue dye exclusion and XTT assays. Treating HL 60 cells with docetaxel and paclitaxel resulted in dose and time dependent cytotoxicity. Docetaxel induced the decrease in the activity of protein phosphatase 1 (PP1) and increase in the activity of PP2 subgroups, while paclitaxel induced the increase in the activity of PP1 and decrease in the activity of PP2 subgroups. Potential use of specific protein phosphatase inhibitors or activators in combination with taxoids will open new windows in the treatment of myeloid leukemias.
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PMID:The interaction between taxoids and serine/threonine protein phosphatase activities during taxan-induced apoptosis of HL 60 leukemic cells. 1879 47

The aim of this study was to investigate the cytotoxic and apoptotic effects of zoledronic acid (ZA) in combination with serine/threonine protein phosphatase inhibitors, calyculin-A (CA) and okadaic acid (OA), in human MCF-7 and MDA-MB-231 breast cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. DNA fragmentation and caspase-3/7 activity assays were performed to evaluate apoptosis. Activities of phosphatase 1 (PP1) and phosphatase 2A (PP2A) were measured by serine/threonine phosphatase ELISA kit. Expression levels of PI3K, p-PI3K, Akt, p-Akt, Bcl-2, p-Bcl-2, Bad, and p-Bad proteins were evaluated by Western blot analysis. Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis as compared to any agent alone in both MCF-7 and MDA-MB-231 breast cancer cells. Combination treatment also resulted in inhibition of both PP1 and PP2A activities. Both agents used alone or in combination did not induce significant changes in total PI3K, Akt, Bcl-2, and Bad expressions, while p-PI3K, p-Akt, p-Bcl-2, and p-Bad levels were reduced by the combination treatment as compared to agents alone. Moreover, apoptotic effect of combination treatment was significantly inhibited in the presence of LY294002, a specific PI3K inhibitor, in both breast cancer cell lines. In conclusion, synergistic apoptotic effect of the combination treatment is correlated with the block of the PI3K/Akt signal pathway in breast cancer cells.
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PMID:Combination of zoledronic acid and serine/threonine phosphatase inhibitors induces synergistic cytotoxicity and apoptosis in human breast cancer cells via inhibition of PI3K/Akt pathway. 2646 35