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)

This is the first study to demonstrate that the small-molecule Bcl-2 inhibitor HA14-1 renders human cervical cancer cells and their Bcl-2 overexpressing radioresistant counterparts, but not normal fibroblasts, more susceptible to heavy ions. Thus, Bcl-2 may be an attractive target for improving the efficacy of heavy-ion therapy.
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PMID:The small-molecule Bcl-2 inhibitor HA14-1 sensitizes cervical cancer cells, but not normal fibroblasts, to heavy-ion radiation. 1877 94

Pinus massoniana bark extract (PMBE) contains a variety of flavonoids whose antioxidant properties have been confirmed in vitro. This study was undertaken to evaluate the cytotoxic effects and the mechanism of cell death on the PMBE-treated human cervical cancer cell line, HeLa. PMBE treatment led to cell growth inhibition in a dose- and time-dependent manner, and PMBE-induced apoptosis was confirmed by DAPI staining, TUNEL assays and sub-G1 phase accumulation. Cell cycle was also arrested in G2/M phase. Immunoblotting analysis showed that cytochrome c was released, the protein expression of Bax was increased, the protein expression of Bcl-2 was down-regulated and caspase-9 and -3 were activated in PMBE-treated HeLa cells. Taken together, PMBE inhibited proliferation, induces apoptosis and causes cell cycle arrest in HeLa cells, indicating that PMBE may be a potential therapeutic agent for cancer.
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PMID:Involvement of the Bcl-2 family members in Pinus massoniana bark extract induced apoptosis in HeLa cells. 1880 51

Cervical cancer still remains a major health problem in women worldwide. Inhibitors of topoisomerase I have proven to be among the most promising new classes of anti-neoplastic agents introducing into the clinic in recent years. CPT-11 is one of the most widely used Camptothecin analogues and is converted to form the active metabolite SN-38. The study tried to explore the in vitro mechanisms of apoptosis induced by SN-38 in cervical cancer cell lines HeLa and SiHa. The results demonstrated here that SN-38 inhibited cell proliferation in a time- and dose-dependant manner. Western Blot showed that SN-38 down-regulated protein expression of p-Akt and increased protein expression of p53 and p21, but it had no effects on protein expression of Bax, Bcl-2 and Akt. Transfection of the full-length Akt cDNA into HeLa and SiHa cells resulted in the reduction of apoptosis induced by SN-38, and Akt kinase activity regulated the p53 pathway, indicating that inhibition of the Akt pathway played an important role in exhibition of SN-38-mediated cytotoxic effect. Our data suggested that SN-38 could induce apoptosis through a p53 pathway and that activation of p53 in response to S-38 is governed by Akt.
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PMID:Inhibition of Akt signaling by SN-38 induces apoptosis in cervical cancer. 1892 42

Exposure of cells to ionizing radiation induces activation of multiple signaling pathways that play critical roles in determining cell fate. However, the molecular basis for cell death or survival signaling in response to radiation is unclear at present. Here, we show opposing roles of the c-jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways in the mitochondrial cell death in response to ionizing radiation in human cervical cancer cells. Ionizing radiation triggered Bax and Bak activation, Bcl-2 down-regulation, and subsequent mitochondrial cell death. Inhibition of JNK completely suppressed radiation-induced Bax and Bak activation and Bcl-2 down-regulation. Dominant-negative forms of stress-activated protein kinase/extracellular signal-regulated kinase kinase 1 (SEK-1)/mitogen-activated protein kinase kinase-4 (MKK-4) inhibited JNK activation. Radiation also induced phosphoinositide 3-kinase (PI3K) activation. Interestingly, inhibition of PI3K effectively attenuated radiation-induced mitochondrial cell death and increased clonogenic survival. Inhibition of PI3K also suppressed SEK-1/MKK-4 and JNK activation, Bax and Bak activation, and Bcl-2 down-regulation. In contrast, inhibition of p38 MAPK led to enhanced Bax and Bak activation and mitochondrial cell death. RacN17, a dominant-negative form of Rac1, inhibited p38 MAPK activation and increased Bax and Bak activation. Exposure of cells to radiation also induced selective activation of c-Src among Src family kinases. Inhibition of c-Src by pretreatment with Src family kinase inhibitor PP2 or small interfering RNA targeting of c-Src attenuated radiation-induced p38 MAPK and Rac1 activation and enhanced Bax and Bak activation and cell death. Our results support the notion that the PI3K-SEK-1/MKK-4-JNK pathway is required for the mitochondrial cell death in response to radiation, whereas the c-Src-Rac1-p38 MAPK pathway plays a cytoprotective role against mitochondrial cell death.
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PMID:Opposing roles of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in the cellular response to ionizing radiation in human cervical cancer cells. 1901 Aug 20

The mechanisms of apoptosis induced by diallyl disulfide (DADS) were explored in human cervical cancer Ca Ski cells. Flow cytometric analysis, DNA gel electrophoresis and DAPI staining demonstrated that DADS induced apoptosis in Ca Ski cells. DADS induced apoptosis through the production of reactive oxygen species and Ca2+, and induced abrogation of mitochondrial membrane potential (Deltapsim) and cleavage of Bid protein (t-Bid). DADS increased the levels of p53, p21 and Bax, but caused a decrease in the level of Bcl-2. DADS also promoted the activities of caspase-3 leading to DNA fragmentation, thus indicating that DADS-induced apoptosis is caspase-3 dependent. In addition, DADS induced an increase in the level of cytochrome c in the cytoplasm, which was released from mitochondria. BAPTA attenuated the Deltapsim abrogation and significantly diminished the occurrence of DADS-induced apoptosis in Ca Ski cells. In conclusion, DADS-induced apoptosis occurs via production of ROS and caspase-3 and a mitochondria-dependent pathway in Ca Ski cells.
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PMID:Diallyl disulfide (DADS) induces apoptosis in human cervical cancer Ca Ski cells via reactive oxygen species and Ca2+-dependent mitochondria-dependent pathway. 1903 12

Phenylacetate induced tumor cytostasis and differentiation. The chemotherapeutic function of the compound in lung cancer has been previously reported, however, whether or not phenylacetate performs other activities is not known. In this study, the potential usage of synthetic phenylacetate derivatives, 4-fluoro-N-butylphenylacetamides (H6) was investigated in human cervical cancer cells. H6 displayed anti-proliferative and apoptosis effects, with an IC(50) of 1.0-1.5 mM and an ID(50) of about 3days. Moreover, it significantly induced apoptosis as evidenced by morphological changes, DAPI and TUNEL staining and DNA fragmentation. H6 increased the expression of Bax protein, whereas it decreased the expression of Bcl-2 protein. H6 also induced accumulation of cytosolic cytochrome c and activation of caspase cascade (caspase-9 and -3), and then DNA fragmentation and apoptosis occurred. The underlying anti-proliferative mechanism for H6 is likely due to the down-regulation of G2/M-phase association cdks and cyclins and up-regulation of p53 to mediate G2/M-phase arrest. Furthermore, the decrease of Bcl-2 and activation of Bax, caspase-9/caspase-3 may be the effectors of H6-induced apoptosis.
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PMID:4-Fluoro-N-butylphenylacetamide (H6) inhibits cell growth via cell-cycle arrest and apoptosis in human cervical cancer cells. 1905 80

Duchesnea indica (Andr.) Focke has been commonly used to treat cancer in Asian countries for centuries, and recently has been shown to possess anticancer properties in vitro and in vivo. But the underlying mechanism of the anticancer action is unclear, especially in in vivo studies. In this study, we investigated the anticancer effect and associated mechanisms of Duchesnea phenolic fraction (DPF) on cervical cancer in vitro and in vivo. Our results showed that DPF significantly inhibited cervical cancer cell proliferation in dose- and time-dependent manners. DPF induced apoptosis as determined by AO/EB staining, DNA fragmentation and flow cytometry. Some apoptosis correlated proteins were altered following DPF treatment. Bax was up-regulated while Bcl-2 was down-regulated, and the expression ratio of Bax/Bcl-2 was increased. These resulted in the translocation of Bax to mitochondria, the release of cytochrome c from the mitochondria to the cytosol and caspase-3 activation. Concurrently, DPF provoked S phase arrest along with significant down-regulation of S phase-associated proteins, such as cyclin A, cyclin E, cyclin D1 and cdk2. Transplanted U14 cervical cancer mouse model was used to evaluate the antitumor effect of DPF in vivo. Compared with control, DPF treatment markedly prolonged survival of tumor-bearing mice and dose-dependently reduced the tumor weight. DPF could induce apoptosis in tumor tissues as evidenced by increased TUNEL-positive cells, activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. In addition, DPF significantly decreased the expression of cell proliferation markers PCNA and ki67 in tumors. All together, these data sustain our contention that DPF has anticancer properties and merits further investigation as a potential therapeutic agent.
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PMID:Duchesnea phenolic fraction inhibits in vitro and in vivo growth of cervical cancer through induction of apoptosis and cell cycle arrest. 1906 47

Total saponin of Solanum lyratum Thunb (TSSLT), a species of natural biologically active substances isolated from Solanum lyratum Thunb, possesses various bioactivities. It has been proposed that the induction of apoptosis may be the basis of its antitumor activity. However, the molecular mechanism underlying the total saponin-induced apoptotic process remains unknown. In the present study, we describe the anti-proliferative effect of TSSLT on human cervical cancer cells (Hela). The TSSLT induced apoptosis of Hela in a time-dependent manner with an IC50 for cell viability of 6 microg/ml. The TSSLT-induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-like activities, poly (ADP-ribose) polymerase (PARP) cleavage and release of cytochrome c (cyt c) into cytosol. TSSLT activated various caspases such as caspase-3, -8, and -9 (like) activities but not caspase-1 like activity. The cell death was completely prevented by the pan caspase inhibitor benzyloxy carbonyl-Val-Ala-Asp- fluoromethyl-ketone (Z-VAD-FMK). More than 80% cell survival was observed in the presence of a caspase-3 inhibitor. In addition, treatment with TSSLT induced the increase of Bax:Bcl-2 ratio in Hela cells. These results suggest that the induction of apoptosis by TSSLT involves multiple pathways antigen including death receptor and mitochondrial pathway and strongly suggest that the mitochondrial pathway was mediated by low expression of Bcl-2 and upregulation of Bax, release of cyt c and subsequent activation of caspase-3 followed by down stream events leading to apoptotic cell death.
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PMID:Antiproliferative activity of the total saponin of Solanum lyratum Thunb in Hela cells by inducing apoptosis. 1906 47

Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis Georgi. Here, we investigated the antitumor effect of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. We found that after inoculated with the HeLa cells the mice treated with oroxylin A showed a significant decrease of tumor volumes and tumor weight compared with the control. Meanwhile, the growth inhibition of oroxylin A on HeLa cells were observed by MTT assay and the value of IC(50) was 19.4+/-0.7 microM after treatment for 48h. Upon our previous research, the inhibition by oroxylin A might be through apoptosis. Then apoptosis induced by oroxylin A in HeLa cells was characterized by DAPI staining and Annexin V/PI double staining, and degradation of PARP (poly-ADP-ribose polymerase) was both found in HeLa cells and tumor tissue. Next, activation of the caspase cascade for both the extrinsic and intrinsic pathways were demonstrated in vivo and in vitro, including caspase-8, -9 and -3. We also found that the expression of Bcl-2 protein decreased, which leading to an increase of the Bax/Bcl-2 ratio. Our results showed that oroxylin A exhibited strong antitumor effect in HeLa cell line and apoptosis induction involved in it.
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PMID:Apoptosis induction of oroxylin A in human cervical cancer HeLa cell line in vitro and in vivo. 1913 24

Cervical cancer is the most common cancer in Indian females and is associated with infection with high risk Human papillomaviruses (HPVs). Curcumin (Diferuloyl methane), a chemopreventive agent, is a natural compound extracted from Curcuma longa that allows suppression of carcinogenesis. The objective of this study was to identify the molecular mechanism of curcumin induced apoptosis in HPV positive cervical cancer HeLa, SiHa and Ca Ski cells. Curcumin causes distinct inhibition of human telomerase reverse transcriptase (hTERT) the catalytic core of telomerase thereby reducing proliferation of cancer cells. Curcumin mediated apoptosis in these cells appears to be due to upregulation of proapoptotic Bax, AIF, release of cytochrome c and down regulation of antiapoptotic Bcl-2, Bcl-XL in HeLa and SiHa. This was accompanied by an increase in caspase-3 and -9 activity, suggesting the role of mitochondria in curcumin mediated apoptotic cell death. Curcumin acts as an anti-inflammatory and anti-proliferative agent by causing down regulation of COX-2, iNOS and cyclin D1 in all the three cell lines but to different extent.
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PMID:Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells. 1919 Oct 10


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