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)

TRIP-Br1 and TRIP-Br2 are potent cell growth promoting factors that function as components of the E2F1/DP1 transcription complex to integrate positive growth signals provided by PHD zinc finger- and/or bromodomain-containing transcription factors. TRIP-Br1 has been demonstrated to be an oncogene. We recently reported that antagonism of the TRIP-Br integrator function by synthetic decoy peptides that compete with TRIP-Br for binding to PHD zinc finger- and/or bromodomain-containing proteins elicit an anti-proliferative effect and induces caspase-3-independent sub-diploidization in cancer cells in vitro. We now demonstrate the chemotherapeutic potential of TRIP-Br decoy peptides for the treatment of cutaneous and intracavitary lesions in vitro as well as in vivo in representative human nasopharyngeal cancer (CNE2), cervical cancer (Ca Ski) and melanoma (MeWo) cancer cell lines. In vitro, BrdU incorporation, colony formation assays and cell cycle analysis confirmed that TRIP-Br decoy peptides possess strong anti-proliferative effects and induce nuclear sub-diploidization in cancer cells. In vivo, CNE2, Ca Ski and MeWo-derived chick embryo chorioallantoic membrane (CAM) tumor xenografts were used to evaluate the effect of topically applied TRIP-Br peptides. Confocal microscopy and flow cytometric analysis demonstrated that cells comprising the tumor xenografts efficiently internalized topically applied FITC-labeled peptides. Fifty muM of TRIP-Br1 decoy peptide significantly suppressed the growth of NPC2-derived human nasopharyngeal tumors, while 50 muM of TRIP-Br2 decoy peptide significantly inhibited tumor growth in all three CAM tumor xenograft models. Two hundred muM of TRIP-Br1 decoy peptide significantly inhibited MeWo-derived tumors. These results suggest that the TRIP-Br integrator function may represent a novel chemotherapeutic target for the treatment of human cutaneous and intracavitary proliferative lesions.
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PMID:Exploiting the TRIP-Br family of cell cycle regulatory proteins as chemotherapeutic drug targets in human cancer. 1750 96

Radiotherapy is the primary line of cancer treatment for cervical cancer and is known to induce cell death in tumors. Radiotherapy is however limited by the total dose that can be given without damaging normal tissue. Plumbagin, a naturally occurring naphthaquinone, has been reported to have free radical producing properties. Hence we hypothesized that plumbagin could also have properties that could modify effects of radiation on cervical cancer cells. Radiation in combination with plumbagin may thus have treatment augmenting effects. Results from our studies have shown that a lower dose of radiation in combination with plumbagin could induce apoptosis more effectively compared to a higher dose of radiation alone. Plumbagin in combination with 2 Gy of radiation was very effective in inducing apoptosis, when compared to a higher radiation dose of 10 Gy alone. This combination also showed a fivefold increase in the activation of caspase 3 in C33A cells. Activation of effector caspases confirms that the induction of apoptosis by irradiation and plumbagin involves caspase-dependent pathways. Expression of apoptotic regulatory molecules Bcl-2, Bax and Survivin was also modulated by plumbagin in combination with radiation. In summary, this study shows that a combination of plumbagin and radiation augmented cell growth inhibition compared to higher radiation dose alone, thus indicating that plumbagin may be a potential radiosensitizer acting through the induction of apoptosis.
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PMID:Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway. 1756 42

Although human papillomavirus (HPV) infections are the primary cause of cervical cancer, the molecular mechanism by which HPV induces cervical cancer remains largely unclear. We used two-dimensional electrophoresis with mass spectrometry to study protein expression profiling between HPV16-positive cervical mucosa epithelial H8 cells and cervical cancer Caski cells to identify 18 differentially expressed proteins. Among them, retinoblastoma-binding protein 4 (RbAp48) was selected, and its differentiation expression was verified with both additional cervical cancer-derived cell lines and human tissues of cervical intraepithelial neoplasia and cervical cancer. Suppression of RbAp48 using small interfering RNA approach in H8 cells significantly stimulated cell proliferation and colony formation and inhibited senescence-like phenotype. Remarkably, H8 cells acquired transforming activity if RpAp48 was suppressed, because H8 cells stably transfected with RbAp48 small interfering RNA led to tumor formation in nude mice. In addition, overexpression of RbAp48 significantly inhibited cell growth and tumor formation. This RbAp48-mediated transformation of HPV16 is probably because of the regulation by RbAp48 of tumor suppressors retinoblastoma and p53, apoptosis-related enzymes caspase-3 and caspase-8, and oncogenic genes, including E6, E7, cyclin D1 (CCND1), and c-MYC. In brief, RbAp48, previously unknown in cervical carcinogenesis, was isolated in a global screen and identified as a critical mediator controlling the transforming activity of HPV16 in cervical cancer.
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PMID:RbAp48 is a critical mediator controlling the transforming activity of human papillomavirus type 16 in cervical cancer. 1761 26

Human cervical cancer is potentially lethal, and therefore the development of effective and tolerable therapeutic options is vital. In the present study, the in vitro effect of the synthetized compound JOT01006 (C21H20C1NO4) on human cervical epithelioid carcinoma cell line (HeLa) was examined. The results demonstrated that JOT01006 induced morphological changes and cytotoxicity (decreased the percentage of viable cells) in a dose-dependent manner. JOT01006 induced apoptosis which was analyzed by flow cytometric methods and confirmed by DAPI staining and DNA fragmentation analyzed by DNA gel electrophoresis. JOT01006 also induced reactive oxygen species (ROS) overproduction before causing endoplasmic reticulum (ER) stress which was also confirmed by the increased levels of Grp78 and Gadd153. Western blotting was selected to demonstrate that JOT010006 promoted p53, Bak, PARP, caspase-3 levels and decreased the levels of Bcl-2 and Bcl-xL. Our results also showed that JOT01006 also promoted caspase-12 production followed by apoptosis. The results also showed that JOT01006 inhibited the migration of HeLa cells potentially through inhibition of MMP-2 and -9.
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PMID:Ethyl 2- [N-m-chlorobenzyl- (2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01006) induces apoptosis in human cervical cancer HeLa cells. 1769 46

Berberine, an isoquinoline alkaloid, has been shown to possess anticancer properties in some cancer cell lines. Here, we report that in vitro treatment of cervical cancer Ca Ski cells with berberine decreased the percentage of viable Ca Ski cells in a dose-dependent and time-dependent manner. Berberine enhanced the apoptosis of Ca Ski cells with the induction of a higher ratio of p53 and Bax/Bcl-2 proteins, increased levels of reactive oxygen species (ROS) and Ca2+, disruption of the mitochondrial membrane potential, and promotion of caspase-3 activity. In CaSki cells pretreated with the pan-caspase inhibitor zVAD-fmk, the berberine-induced caspase-3 activity and apoptosis were significantly blocked as confirmed by flow cytometric analysis. Western blot also showed that berberine induced the expression of GADD153, a transcription factor involved in apoptosis. Thus berberine increased ROS levels leading to endoplasmic reticulum (ER) stress based on the increase of GADD153 and shown by Ca2+ release from the ER. When the Ca Ski cells were pretreated with catalase, GADD153 production was abrogated and apoptosis was significantly reduced.
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PMID:GADD153 mediates berberine-induced apoptosis in human cervical cancer Ca ski cells. 1797 84

The effects of coumarin on cell viability, cell cycle arrest and induction of apoptosis were investigated in human cervical cancer HeLa cells. Coumarin was cytotoxic with an IC50 of 54.2 microM, induced morphological changes, and caused G0/G1 arrest and apoptosis. The decreasing number of viable cells appeared to be due to induction of cell cycle arrest and apoptotic cell death, since coumarin induced morphologically apoptotic changes and internucleosomal DNA laddering fragmentation and increased the sub-G1 group. Coumarin affected the production of reactive oxygen species and Ca2+ concentration, and dose-dependently induced the depolarization of mitochondrial membrane potential. Also, coumarin treatment gradually decreased the expression of G0/G1-associated proteins which may have led to the G0/G1 arrest, and the anti-apoptotic proteins Bcl-2 and Bcl-xL, and increased the expression of the pro-apoptotic protein Bax. Coumarin decreased the mitochondrial membrane potential and promoted the release of cytochrome c and the activation of caspase-3 before leading to apoptosis. These results provide information on the mechanisms by which coumarin induces cell cycle arrest and apoptosis in human cervical cancer cells (HeLa).
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PMID:Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation. 1821 Jul 47

Clitocine, a natural biologically active substance isolated from the mushroom Leucopaxillus giganteus, possesses several bioactivities including antitumor. Here, for the first time, we studied the molecular mechanism of clitocine-induced apoptosis in human cervical cancer cells (HeLa). Clitocine-induced cell death was characterized with the changes in cell morphology, DNA fragmentation, activation of caspase-3, -8, and -9 (like) activities, poly(ADP-ribose) polymerase (PARP) cleavage, release of cytochrome c (cyt c) into cytosol, and increase of Bax:Bcl-2 ratio. These results indicated that the induction of apoptosis by clitocine involved the multiple pathway including death receptor and mitochondrial pathways, and strongly suggested that the mitochondrial pathways were mediated by down-regulation of Bcl-2 and up-regulation of Bax, release of cytochrome c and subsequent activation of caspase-3 followed by down stream events leading to apoptotic mode of cell death.
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PMID:Anti-proliferative effect of clitocine from the mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells by inducing apoptosis. 1822 36

Radiotherapy is currently applied in the treatment of human cancers. We studied whether genistein would enhance the radiosensitivity and explored its precise molecular mechanism in cervical cancer cells. After co-treatment with genistein and irradiation, the viability, cell cycle analysis, and apoptosis signaling cascades were elucidated in CaSki cells. The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone. Treatment with only gamma-irradiation led to cell cycle arrest at the G1 phase. On the other hand, co-treatment with genistein and gamma-irradiation caused a decrease in the G1 phase and a concomitant increase up to 56% in the number of G2 phase. In addition, cotreatment increased the expression of p53 and p21, and Cdc2- tyr-15-p, supporting the occurrence of G2/M arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, downregulation of Bcl-2, and activation of caspase-3 and -8 in the treatment of genistein and irradiation. Apparently, co-treatment downregulated the transcripts of E6*I, E6*II, and E7. Genistein also stimulated irradiation-induced intracellular reactive oxygene, species (ROS) production, and co-treatment-induced apoptosis was inhibited by the antioxidant N-acetylcysteine, suggesting that apoptosis has occurred through the increase in ROS by genistein and gamma-irradiation in cervical cancer cells. Gamma-irradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and gamma-irradiation almost completely prevented irradiation-induced COX-2 expression and PGE2 production. Co-treatment with genistein and gamma-irradiation inhibited proliferation through G2/M arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.
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PMID:Sensitization of the apoptotic effect of gamma-irradiation in genistein-pretreated CaSki cervical cancer cells. 1838 72

Single-drop analysis of two different real sample solutions (2 microL) while simultaneously monitoring the activity of two sets of ten different proteases on a single microfluidic device is presented. The device, called a capillary-assembled microchip (CAs-CHIP), is fabricated by embedding square glass sensing capillaries (reagent-release capillaries, RRC) in the polydimethylsiloxane (PDMS) lattice microchannel, and used for that purpose. First, the performance reliability was evaluated by measuring the fluorescence response of twenty caspase-3-sensing capillaries on a single CAs-CHIP, and a relative standard deviation of 1.5-8.2 (% RSD, n = 5 or 10) was obtained. This suggests that precise multiplexed protease-activity sensing is possible by using a single CAs-CHIP with multiple RRCs embedded. Then, using a single CAs-CHIP, real sample analysis of the activity of ten different caspases/proteases in cervical cancer (HeLa) cell lysate treated and untreated with the cell-death-inducer drug, doxorubicin, was simultaneously carried out, and a significant difference in enzyme activity between these two samples was observed. These results suggested the usefulness of the CAs-CHIP in the field of drug discovery.
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PMID:Single-drop analysis of various proteases in a cancer cell lysate using a capillary-assembled microchip. 1843 62

Although it has been previously reported that bee venom (BV) can induce apoptosis in many cancer cell lines, there is no information on the effect of BV on human cervical cancer cells and its molecular mechanisms of action are not fully elucidated. In this study, the possible mechanisms of apoptosis by which BV acts on human cervical cancer Ca Ski cells were investigated. BV induced morphological changes and decreased the percentage of viable Ca Ski cells in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species, increased the level of cytoplasmic Ca2+, reduced mitochondrial membrane potential which led to cytochrome c release, and promoted the activation of caspase-3 which then led to apoptosis. BV also induced an increase in the levels of Fas, p53, p21 and Bax, but a decrease in the level of Bcl-2. The activities of both caspase-8 and caspase-9 were enhanced by BV, promoting caspase-3 activation, leading to DNA fragmentation. Based on the DNA fragmentation and DAPI staining, BV-induced apoptosis was mitochondrial-dependent and caspase-dependent. BV also promoted the expression of AIF and Endo G in the Ca Ski cells. Both AIF and Endo G proteins were released from the mitochondria, and then induced apoptosis which was not through activation of caspase. In conclusion, our data demonstrated that BV-induced apoptosis occurs via a Fas receptor pathway involving mitochondrial-dependent pathways and is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.
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PMID:Bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells. 1850 26


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