Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytotoxic effects of a new compound, ethyl 2-[N-p-chlorobenzyl-(2'-methyl)] aniline-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01007) have been tested in mouse leukemia WEHI-3 cells. In this study, the mechanisms by which JOT01007 acts on a human cervical cancer cell line (Ca Ski) to bring about an increase in the ratio of Bax/Bcl-2, reduction of the mitochondrial membrane potential (MMP), increase in the levels of cytoplasmic Ca2+, activation of caspases and fragmentation of DNA, and apoptosis were investigated. Flow cytometric analysis demonstrated that JOT01007 induced a decrease of MMP in Ca Ski cells. JOT01007 induced an increase in the level of cytoplasmic Ca2+, which was inhibited by BAPTA (calcium chelator), and BAPTA accelerated the MMP reduction, and significantly blocked JOT01007-induced apoptosis. Western blotting demonstrated that JOT01007 induced an increase in the levels of p53, p2I, cytochrome-c, caspase-3 and Bax, but decreased the level of Bcl-2. In conclusion, our data demonstrate that JOT01007-induced apoptosis occurs via a mitochondria-dependent pathway closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.
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PMID:Ethyl 2- [N-p-chlorobenzyl- (2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01007)induces apoptosis in human cervical cancer Ca Ski cells. 1743 94

Infection with human papillomaviruses (HPV), and suppression of apoptosis and cell adhesion are putative aetiological factors to cervical carcinogenesis. However, controversial results have been reported with respect to their relationships with cervical carcinomas. Here we analysed papillomavirus infection, apoptotic index (AI), expressions of the anti-apoptotic proteins Bcl-2 and Survivin, and expression of the cell-adhesion protein CD44 in cervical tissue samples from individuals with and without cervical carcinomas. Although both HPV16 and HPV18 are reportedly important aetiological factors, we found that cervical carcinomas were highly associated with HPV16 but not HPV18 infection. Immunohistochemistry showed that the percentages of cells expressing Bcl-2, Survivin, and CD44v6 were greatly increased in samples of cervical carcinomas. Furthermore, the expression rates of Survivin and CD44v6 increased whereas that of Bcl-2 declined as cervical cancers developed into more advanced clinical or histopathological stages. Surprisingly, there was little difference in AI between control and cervical cancer samples. These observations provide further evidence that HPV infection, apoptosis and cell adhesion abnormalities are related to cervical cancers. They also suggest that Bcl-2, Survivin and CD44v6 expressions, and HPV16 infection could be useful indices in screening of cervical carcinomas.
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PMID:Analyses of Bcl-2, Survivin, and CD44v6 expressions and human papillomavirus infection in cervical carcinomas. 1746 68

Solanum nigrum Linne (SNL) has been used in traditional Chinese medicine for centuries because of its diuretic and antipyretic effects. The present study examined the effect of the crude polysaccharides isolated from Solanum nigrum Linne (SNL-P) on tumor growth. SNL-P had a significant growth inhibition effect on cervical cancer (U14) of tumor-bearing mice. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly, the expression of Bax increased and the expression of Bcl-2 and mutant p53 decreased dramatically in cervical cancer sections after oral administration of SNL-P for 12 days. Moreover, SNL-P treatment decreased the level of blood serum TNF-alpha. These results indicated that the tumor growth inhibition of SNL-P administration might correlate with the reduction of TNF-alpha level of blood serum, which resulted in a massive necrosis in tumor tissues and the up-regulation of Bax and down-regulation of Bcl-2 and mutant p53 gene expression, which triggered apoptosis in tumor cells. These findings demonstrated that the SNL-P is a potential antitumor agent.
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PMID:Antitumor activity of crude polysaccharides isolated from Solanum nigrum Linne on U14 cervical carcinoma bearing mice. 1748 83

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

Pinus koraiensis Bark Procyanidins Extract (PKBPE) has been used in traditional Chinese medicine for thousands of years. In this study, we determined PKBPE effect on tumor weight, SOD (superoxidate dismutase) activity, the content of MDA (malondialdehyde) through colorimetric analysis antigenic, and expression of Ki-67, p53 and Bcl-2 on mice bearing U14 cervical cancer. Treatment with PKBPE (158 and 250 mg/kg body weight, p.o.) could inhibit U14 cervical carcinoma growth up to 47.68 and 58.94%. In addition, PKBPE enhance the activity of SOD (p<0.01) and decrease MDA content. Furthermore, we also observed that PKBPE treatment significantly inhibited the expression of Ki-67, mutant p53 and Bcl-2 protein (p<0.01). The results suggested that PKBPE showed antitumor activities on U14 cervical carcinoma mice. The mechanism of PKBPE antitumor activity might be associated with free radical production inhibition and regulation of the expression of Ki-67, mutant p53 and Bcl-2 protein.
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PMID:Antitumor activity of the procyanidins from Pinus koraiensis bark on mice bearing U14 cervical cancer. 1760 74

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

Saponin extracted from Patrinia villosa (Thunb.) Juss (SPVJ) is a Chinese medicine which is used widely by traditional medicine doctors. In this study, the antitumor effects and the possible mechanisms of SPVJ were investigated in mice bearing U14 cervical cancer. The results showed that SPVJ (50 mg/kg and 100 mg/kg) effectively reduced the weight of U14 cervical tumor (35.1% and 57.1%, respectively). Compared with the control group, SPVJ (100 mg/kg) significantly increased tumor cells in the G0/G1 phase (38.1% vs 68.5%), increased the number of cells in apoptosis (9.4% vs 28.9%) and G0/G1 phase and decreased the number of cells in S phase (41% vs 26.2%) and G2/M (20.9% vs 5.3%), inhibited proliferating cell nuclear antigen (PCNA) of tumor cell (80.6% vs 21.8%), decreased the expression of mutant p53 (66.4% vs 33.5%) and bcl-2 protein (78.2% vs 20.3%). The mechanism of the SPVJ antitumor effect might be associated with inhibition of tumor cells in G0/G1 phase, inducing apoptosis and inhibiting the expression of PCNA, mutant P53 and Bcl-2 protein.
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PMID:Antitumor effects of saponin extract from Patrinia villosa (Thunb.) Juss on mice bearing U14 cervical cancer. 1835 May 12


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