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

DNA topoisomerase inhibitors induce a specific signaling cascade that promotes an active apoptotic caspase-dependent cell death process. However, little is known about the initial signals elicited by these agents. In the present study, we compared apoptosis in HL-60 cells treated either with the chemotherapeutic drug etoposide (VP16) alone or combined with the broad caspase inhibitor ZVAD.fmk. Apoptosis was assessed by changes in cell morphology and agarose gel electrophoresis of extracted cell DNA. We found that ZVAD.fmk prevents VP16-induced DNA fragmentation and the appearance of an increased number of apoptotic cells in the culture. We also compared the effects of etoposide alone or together with the pan-caspase inhibitor ZVAD.fmk on proliferating cell nuclear antigen, Bcl-2, and actin expression in human promyelocytic leukemia HL-60 cells. In addition, we screened for proteins that were initially upregulated in a caspase-dependent manner. Indeed, some proteins were induced in the cytoplasm and subsequently accumulated in the nuclei after etoposide treatment. This process was slightly inhibited by the caspase inhibitor ZVAD.fmk. We suggest that these proteins are associated with the induction of specific signaling cascades that characterize the apoptotic cell death process.
 ...
PMID:Alterations in protein expression in HL-60 cells during etoposide-induced apoptosis modulated by the caspase inhibitor ZVAD.fmk. 1565 22

The biological activities of Moxa, used as moxibustion, have not been well documented. We investigated here Moxa smoke for its tumor-specific cytotoxicity, anti-HIV activity, radical intensity and radical scavenging activity, in comparison with previously published data of Moxa extract. Moxa smoke showed slightly higher cytotoxicity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, promyelocytic leukemia HL-60) than against normal oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), yielding a tumor specificity index of 1.29. Moxa smoke dose-dependently induced internucleosomal DNA fragmentation, activation of caspases 3, 8 and 9, and slightly modified the expression of apoptosis-related proteins (Bcl-2, Bad, Bax) in HL-60 cells, but to much lesser extents than attained by positive controls (UV irradiation, actinomycin D treatment). ESR spectroscopy showed that Moxa smoke generated semiquinone-type radicals under alkaline conditions, and scavenged O2(-), hydroxyl radical, singlet oxygen and NO. All Moxa smoke preparations showed no apparent anti-HIV activity. These data demonstrate the antitumor potential of Moxa smoke.
 ...
PMID:Cytotoxicity and radical modulating activity of Moxa smoke. 1579 3

2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a metabolite of benzene, induces apoptosis in human promyelocytic leukemia (HL-60) cells. However, the mechanisms by which TGHQ induces apoptosis are unclear, and they were the focus of the present investigation. TGHQ stimulated the rapid formation (30 min) of reactive oxygen species (ROS) in HL-60 cells, and co-treatment with catalase or the antioxidant N-acetylcysteine (NAC) completely blocked TGHQ-induced apoptosis, implicating a causative role for ROS in HL-60 cell death. Western blot analysis revealed the complete disappearance of pro-caspase 9 between 1 and 2 hours after exposure of HL-60 cells to TGHQ, concomitant with the appearance of cleaved caspase 9 and increases in caspase 9 activity. The appearance of two cleaved forms of caspase 3 occurred subsequent to increases in caspase 9 activity. Levels of the anti-apoptotic Bcl-2 protein remained constant during TGHQ-induced apoptosis of HL-60 cells, but Bcl-2 S70 phosphorylation decreased. In contrast, changes in the subcellular localization of the pro-apoptotic molecule Bax were observed, with a rapid (15-60 min) increase in the ratio of cytosolic to mitochondrial Bax. Cytochrome c release from mitochondria to the cytosol occurred after Bax translocation and the dephosphorylation of pS70 Bcl-2. However the mitochondrial inner transmembrane potential (deltapsi(m)) was maintained, even after cytochrome c was released from the mitochondria. Cyclosporin A, an inhibitor of the mitochondrial membrane permeability transition pore (PTP), did not completely rescue HL-60 cells from apoptosis. Taken together, we conclude that TGHQ facilitates ROS production, alters the post-translational modification of Bcl-2 and subcellular localization of Bax, culminating in the release of cytochrome c and caspase activation.
 ...
PMID:2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ)-mediated apoptosis of human promyelocytic leukemia cells is preceded by mitochondrial cytochrome c release in the absence of a decrease in the mitochondrial membrane potential. 1580 30

Thrombospondin-1 (TSP-1) is a multifunctional adhesive glycoprotein that is synthesized by several cell types and modulates cell growth and differentiation. In this study, we showed that the amount of TSP-1 secreted by two human leukemia cell lines, HL-60 and NB4, increased markedly during differentiation of these cells by all-trans retinoic acid (ATRA) (10(-7) M), reaching about 100 ng/10(6) cells after 3 days. Addition of purified TSP-1 alone (10(-9)-5 x 10(-8) M) to HL-60 or NB4 cell cultures dose-dependently inhibited cell growth and differentiation. Differently to ATRA, TSP-1-induced differentiation of HL-60 and NB4 cells occurred independently of Bcl-2 regulation, as shown by immunofluorescence and Western immunoblotting. At day 5, TSP-1 also induced promyelocytic leukemia cell apoptosis. The percentage of apoptotic cells in NB4 cultures was higher with TSP-1 (5 x 10(-8) M) than with ATRA (10(-7) M) (46+/-3% versus 19+/-7%, p<0.001), whereas similar levels of apoptosis (37+/-7% and 38+/-6%) were reached with both agents in HL-60 cultures. Studies performed with synthetic peptides derived from the TSP-1 sequence indicated that two heparin-binding peptides, Hep-I and GGWSHW, located within the NH2-terminal and type 1 repeats respectively, were strong inducers of apoptosis of HL-60 and NB4 cells, suggesting that cell surface heparan sulfate molecules might be involved in the apoptotic effect of TSP-1 on promyelocytic cells.
 ...
PMID:Thrombospondin-1 (TSP-1) and TSP-1-derived heparin-binding peptides induce promyelocytic leukemia cell differentiation and apoptosis. 1586 7

Doxorubicin (adriamycin), an anthracycline antibiotic, showed higher cytotoxic activity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60) than against normal human cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF). Doxorubicin activated caspases 3, 8 and 9 in both HSC-2 and HL-60 cells, but induced internucleosomal DNA fragmentation only in HL-60 cells. Western blot analysis showed that doxorubicin did not significantly change the intracellular concentration of Bcl-2, Bax and Bad in HL-60 cells. Real-time PCR analysis showed that HPC cells expressed the highest amount of mdr1 mRNA, followed by HSC-2 > HGF > HSC-3 > HPLF > HSG > HL-60. ESR spectroscopy showed that doxorubicin produced no discernible radical under alkaline conditions (pH 7.4 to 10.5) except at pH 12.5, and it did not scavenge O2-, NO and DPPH radicals. The present study demonstrates that doxorubicin induces the tumor-specific cytotoxicity and some, but not all, apoptosis markers possibly by a radical-independent mechanism, and that mdr1 expression in the tumor cells is not related to the tumor specificity of doxorubicin.
 ...
PMID:Induction of tumor-specific cytotoxicity and apoptosis by doxorubicin. 1586 24

The polysaccharide peptide (PSP) isolated from the mycelia of Chinese Medicinal fungus Coriolus versicolor has proven benefits in clinical trials in China but the mechanism of action has not been elucidated. In this study, HL-60 cell line was used to investigate the anti-proliferation and cell death process of PSP. The cytotoxicity of PSP on normal human T-lymphocytes was also evaluated. We show that PSP induced apoptosis of human promyelocytic leukemia HL-60 cells but not of normal human T-lymphocytes. The apoptotic machinery induced by PSP was associated with a decrease in Bcl-2/Bax ratio, drop in mitochondrial transmembrane potential, cytochrome c release, and activation of caspase-3, -8 and -9. Activation of the cellular apoptotic program is a current strategy for the treatment of human cancer, and the selectivity of PSP to induce apoptosis in cancerous and not on normal cells supports its development as a novel anticancer agent.
 ...
PMID:The cell death process of the anticancer agent polysaccharide-peptide (PSP) in human promyelocytic leukemic HL-60 cells. 1587 Sep 43

The purpose of the present study was to investigate the anti-proliferative and apoptotic effects of MCS-C2, a novel synthetic analogue of the pyrrolo[2,3-d]pyrimidine nucleoside toyocamycin and sangivamycin, in human promyelocytic leukemia (HL-60) cells. When treated with 5 microM MCS-C2, inhibited proliferation associated with apoptotic induction was found in the HL-60 cells in a concentration-dependent and time-dependent manner, plus nuclear DAPI staining revealed the typical nuclear features of apoptosis. However, MCS-C2 showed almost no antiproliferative effect and no apoptotic induction in normal lymphocyte cells used as a control when compared with those in HL-60 cancer cells. Moreover, a flow cytometric analysis of the HL-60 cells using FITC-dUTP and propidium iodide (PI) showed that the apoptotic cell population increased gradually from <1% at 0 h to 34% at 12 h after exposure to 5 microM MCS-C2. This apoptotic induction was associated with the cleavage of Bid and a release of cytochrome c from mitochondria into the cytosol, followed by the activation of caspase-3 and inactivation of poly(ADP-ribose) polymerase (PARP). However, there was no significant change in any other mitochondrial membrane proteins, such as Bcl-2 and Bax. Consequently, the current findings suggest that the mitochondrial pathway was primarily involved in the MCS-C2-induced apoptosis in the human promyelocytic leukemia HL-60 cells.
 ...
PMID:Induction of apoptosis in human leukemia cells by MCS-C2 via caspase-dependent Bid cleavage and cytochrome c release. 1589 58

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the only non-steroidal anti-inflammatory drug so far which has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis. The molecular mechanism responsible for the anti-cancer effects of celecoxib is not fully understood. There is little data on the potential role of COX-2 in lymphoma pathogenesis. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of celecoxib on human chronic myeloid leukemia cell line, K562 and other hematopoietic cancer cell lines like Jurkat (human T lymphocytes), HL60 (human promyelocytic leukemia) and U937 (human macrophage). Treatment of these cells with celecoxib (10-100 microM) dose-dependently, reduced cell growth with arrest of the cell cycle at G0/G1 phase and induction of apoptosis. Further mechanism of apoptosis induction was elucidated in detail in K562 cell line. Apoptosis was mediated by release of cytochrome c into the cytoplasm and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). This was followed by DNA fragmentation. The level of anti-apoptotic protein Bcl-2 was decreased without any change in the pro-apoptotic Bax. Celecoxib also inhibited NF-kB activation. Celecoxib thus potentiates apoptosis as shown by MTT assay, cytochrome c leakage, PARP cleavage, DNA fragmentation, Bcl-2 downregulation and possibly by inhibiting NF-kB activation.
 ...
PMID:Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia in vitro. 1591 Oct 99

1-(3,4-dimethoxyphenyl)-3,5-dodecenedione (I6), a gingerdione derivative, was synthesized in our laboratory, has been demonstrated to be an effective anti-tumor agent in human leukemia cells. Gingerdione is one of the components from ginger. In the present study, we found that I6 could inhibit cell proliferation in the time- and dose-dependent manner in human promyelocytic leukemia HL-60 cells. To investigate the anti-proliferation mechanism of I6, cell cycle analysis was performed. Results showed that I6 induced significant G1 arrest and apoptosis in HL-60 cells. It was proved by the reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of regulatory on G1 arrest that the levels of p15 and p27 increased after treatment and mRNA levels of cyclin D2, cyclin E, and cdc25A were decreased. The I6-induced apoptosis was further confirmed by DNA fragmentation assay. The DNA gel electrophoresis showed that I6 induced DNA fragmentation, a biochemical hallmark of apoptosis, in HL-60 cells. I6-induced apoptosis was accompanied by an apparent up-regulation of caspase-3, and down-regulation of Bcl-2. Taken together, these results suggest that markedly down-regulation of G1 associated cyclin D2, cyclin E and cdc25A and up-regulation of CDKI, p15 and p27, and may contribute to I6-mediated cell cycle arrest. Furthermore, the Bcl-2 expression decrease and caspase-3 activation may be the plausible mechanism by which I6 induced apoptosis. These results suggest that I6 is a potent anti-HL-60 drug and possess a significant action on cell cycle before commitment for apoptosis occurrence.
 ...
PMID:1-(3,4-dimethoxyphenyl)-3,5-dodecenedione (I6) induces G1 arrest and apoptosis in human promyelocytic leukemia HL-60 cells. 1592 54

Terbinafine (TB, lamisil), a promising world widely used oral-anti-fungal agent, has been used in the treatment of superficial mycosis. In this study, we found that apoptosis but not cell growth arrest was induced by TB (1 microM, for 24 h) in human promyelocytic leukemia (HL60) cells. The apoptotic effect induced by TB in the HL60 cell was not through the general differentiation mechanisms evidenced by evaluation of three recognized markers, including CD11b, CD33, and morphological features. In addition, our results also revealed that TB-induced apoptosis was not through the cellular surface CD 95 receptor-mediated signaling pathway. We found that the mitochondria membrane in the TB-treated HL60 cells was dissipated by decreasing of the electrochemical gradient (DeltaPsi(m)) led to leakage of cytochrome c from mitochondria into cytosol. Such effects were completely blocked by in vitro transfection of the HL60 cells with Bcl-2 overexpression plasmid (HL60/Bcl-2). However, our data found that TB-mediated apoptosis could not be completely prevented in the Bcl-2 over expressed (HL60/Bcl-2) cells. Such results implied that additional mediators (such as caspase-9) other than mitochondria membrane permeability might contribute to the TB-induced cellular apoptosis signaling. This hypothesis was supported by the evidence that administration of caspases-9 specific inhibitor (z-LEHD-fmk) blocked the TB-induced apoptosis. Our studies highlight the molecular mechanisms of TB-induced apoptosis in human promyelocytic leukemia (HL60) cells.
 ...
PMID:Involvement of proapoptotic Bcl-2 family members in terbinafine-induced mitochondrial dysfunction and apoptosis in HL60 cells. 1612 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>