UNIPROT:P10415 - FACTA Search

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)

Introduction of bcl-2 gene in EIA + c-Ha-ras-transformed rat embryo fibroblasts, which are unable to be arrested after damaging influences and possess high proapoptotic sensitivity, results not only in suppression of cell death but also in re-establishment of cell cycle block following DNA damage and serum starvation. Flow cytometry showed that E1A + c-Ha-ras + bcl-2-transformants treated with DNA-intercalator adriamycin are capable of being arrested at G1/S boundary for a long time (for less than 5 days). According to the growth curve data, the number of Bcl-2-overexpressing cells remanins constant for a week of cultivation with adriamycin. Clonogenic efficacy of E1A + c-Ha-ras + bcl-2-cells is brought to no already in 16 h after adriamycin addition. Apoptotic death, revealed by oligonucleosomic fragmentation of DNA, as well as cell death, occurring due to mitotic catastrophe, after adriamycin treatment are almost absent in Bcl-2-overexpressing transformants, as compared with parental E1A + c-Ha-ras-transformants. Bcl-2 introduction in E1A + c-Ha-ras-transformants is accompanied by a rise of SA beta-Gal (Senescence Associated beta-Galactosidase) activity, which is commonly considered to be a marker of cell senescence. Adriamycin treatment of E1A + c-Ha-ras + bcl-2-transformants results in a much higher rise in SA beta-Gal activity, as compared with untreated cells. Co-immunoprecipitation experiments demonstrated the introduction of Bcl-2 to result in formation of Bcl-2 complexes with early region E1A oncoproducts, which are thought to be responsible for proapoptotic susceptibility of E1A-expressing transformants. The data obtained lead to suggestion that bcl-2 transfer to E1A + c-Ha-ras-transformants may induce a switch from the cell death program on the program of senescence after DNA damage, due, presumably, to Bcl-2 interaction with the apoptosis activator the viral oncoprotein E1A.
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PMID:[Antiapoptotic oncogene bcl-2 induces a program of senescence in E1A + c-Ha-ras-transformants treated with adriamycin]. 1671 90

Adriamycin is a potent antitumor drug that is known to cause severe cardiotoxicity. This study examined the protective effect of calceolarioside on adriamycin-induced cardiomyocyte toxicity. Calceolarioside significantly inhibited the adriamycin induced cell death and caspase-3 activation, which may be explained by the increase in Bcl-2 expression and the inhibition of Bax expression. Calceolarioside increased the expression of the antioxidant molecules and decreased the level of intracellular reactive oxygen species. Catalase, glutathione, N-acetylcysteine, Mannitol and Mn-TBAP (manganese (III) tetrakis-(4-benzoic acid) porphyrin) significantly inhibited the H9c2 cell death induced by adriamycin. Calceolarioside significantly inhibited H9c2 cell death, and was more effective than that observed with the other antioxidants, including probucol, ascorbic acid, and alpha-tocopherol. Overall, these results suggest that calceolarioside can inhibit adriamycin-induced apoptosis in H9c2 cardiomyocyte by inhibiting the generation of reactive oxygen species. Calceolarioside may be a potential candidate agent that inhibits cardiomyocyte-toxicity in adriamycin-exposed patients.
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PMID:Protective effect of calceolarioside on adriamycin-induced cardiomyocyte toxicity. 1678 Aug 32

Adriamycin is an effective anthracycline anti-tumor antibiotic. However, the clinical use of adriamycin has been restricted by its serious side effects. Some reports indicated that the side effects of adriamycin could cause systemic injury, in which reactive oxygen species (ROS) play an important role. ROS are a large family of oxygen free radical and non-free radical active oxygen-containing molecules, including superoxide radical, hydrogen peroxide and hydroxyl radical, which contribute to oxidative stress. Although antioxidant treatment is a promising method to prevent the side effects, protection by a single antioxidant is limited. The Chinese herbal medicine ANTIOXIN is a multiple antioxidant that can effectively block oxidative stress. It was hypothesized that ANTIOXIN could effectively reduce the side effects of adriamycin. A rat tumor model with a transplanted tumor in the liver was treated with adriamycin and ANTIOXIN was used as a protection. Oxidative stress and antioxidant enzymes were evaluated. The results showed that adriamycin chemotherapy increased the level of malondialdehyde (MDA), nitrogen oxide (NO) and decreased the activities of total superoxide dismutase (T-SOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione (GSH) and total antioxidant capacity (TAC). Adriamycin chemotherapy also decreased the expression of Bcl-2, increased the expression of iNOS and cell apoptosis in the liver and kidney. Multiple antioxidants ANTIOXIN had an antagonistic effect on these changes and significantly decreased the mortality of the experimental rats. These data demonstrated that adriamycin chemotherapy could cause oxidative stress to the whole body, on which multiple antioxidants based on the theory of 'multiple antioxidant chain' had effective protection.
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PMID:Protection of multiple antioxidants Chinese herbal medicine on the oxidative stress induced by adriamycin chemotherapy. 1758 87

This study was purposed to investigate the inhibitory effect, apoptosis, Bcl-2 and P-gp expression of K562/AO2 cells by hyperthermia combined with adriamycin. The working concentration of adriamycin against K562/AO2 was determined by MTT assay. The hyperthermia and chemotherapy were used alone or in combination, then the cell survival rate was detected at 48 hours. The inhibitory effect was evaluated by MTT assay. The apoptosis rate, Bcl-2 and P-gp expression of K562/AO2 were determined by flow cytometry. The concentration of adriamycin in the experiment was defined as its IC(50) at 48 hours action. The results indicated that the hyperthermia at 40, 41 and 42 degrees C for 60 minutes showed obvious inhibitory effect on K562/AO2 cells (p < 0.01). Adriamycin chemotherapy combined with hyperthermia showed more obvious inhibitory effect on K562/AO2. According to flow cytometric analysis, the hyperthermia and adriamycin used alone or in combination could obviously increase the apoptosis rate and down-regulate Bcl-2 and P-gp expression of K562/AO2 cells (p < 0.01). It is concluded that the adriamycin chemotherapy combined with hyperthermia for 60 minutes shows obvious inhibitory effect on K562/AO2 cells, which increases the apoptosis rate and down-regulates expression of Bcl-2 and P-gp.
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PMID:[Effect of hyperthermia in combination with chemotherapy on K562/AO2 cells in vitro]. 1770 91

We investigated the relationship between the resistance to the proapoptotic action of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and cellular prion protein (PrPc) function, using the TRAIL-sensitive MCF-7 human breast adenocarcinoma cell line and two TRAIL-resistant sublines: 2101 and MCF-7/ADR. All of the cell lines tested expressed TRAIL-R1 and TRAIL-R2. TRAIL decoy receptors were not detected, suggesting that the resistance of 2101 and MCF-7/ADR cells, strongly expressing PrPc, to TRAIL-mediated cell death was independent from the expression of TRAIL receptors and death-inducing signaling complex formation. Down-regulation of PrPc by small interfering RNA increased the sensitivity of Adriamycin- and TRAIL-resistant cells to TRAIL, but not to epirubicin/Adriamycin. TRAIL-mediated apoptosis in PrPc knocked-down cells was associated with caspase processing, Bid cleavage, and Mcl-1 degradation. In addition, an increased sensitivity of apoptosis-resistant cells to TRAIL after PrPc silencing was not associated with the increased recruitment of receptors and intracellular signaling molecule to the death-inducing signaling complex. Bcl-2 expression was substantially decreased after PrPc knock-down but the levels of Bcl-X(L) and Mcl-1 were not affected. The down-regulation of Bcl-2 was concomitant with Bax delocalization. Our findings support the notion that silencing of PrPc facilitates the activation of proapoptotic Bax by down-regulation of Bcl-2 expression, thereby abolishing the resistance of breast cancer cells to TRAIL-induced apoptosis.
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PMID:Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death. 1800 36

Tanshinone IIA (TSN) is a monomer extracted from the Chinese herb Danshen. In this study, we examined the effect of Tanshinone IIA on adriamycin (ADR)-induced apoptosis in neonatal rat cardiomyocytes and underlying molecular mechanisms. Primary cultured cardiomyocytes were treated with 1 micromol/L of adriamycin for 24 h with or without pretreatment with Tanshinone IIA (0.5-2 micromol/L) for 2 h. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, and flow cytometry measurement were used to assess cell viability and apoptosis. Fluorescent probes 2',7'-dichlorofluorescein diacetate and dihydroethidium were used to detect the production of reactive oxygen species. Western blotting was used to evaluate the expression of Bcl-2 and Bax proteins. Adriamycin significantly induced apoptosis in cardiomyocytes. Tanshinone IIA (0.5-2 micromol/L) ameliorated apoptosis induced by adriamycin in a dose-dependent manner. Tanshinone IIA (2 micromol/L) markedly attenuated adriamycin-induced reactive oxygen species production. Western blotting revealed that Tanshinone IIA prevented the adriamycin-mediated reduction of the ratio of Bcl-2/Bax. In conclusion, Tanshinone IIA significantly inhibits adriamycin-induced cardiomyocyte apoptosis in a dose-dependent manner, and this effect is at least partly caused by its antioxidant properties.
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PMID:Tanshinone IIA protects neonatal rat cardiomyocytes from adriamycin-induced apoptosis. 1820 75

Expression of the Bcl-2 protein confers resistance to chemotherapy-mediated apoptotic signals in patients with breast cancer. We investigated effects of Bcl-2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide oblimersen in breast tumor biopsies. Oblimersen targets Bcl-2 messenger RNA (mRNA), down-regulates Bcl-2 protein translation and enhances antitumor effects of subtherapeutic chemotherapy doses. Within a phase I trial, we administered escalating doses of oblimersen (3, 5 or 7 mg/kg/day) as continuous infusion on days 1-7 in combination with standard-dose docetaxel (Taxotere), Adriamycin and cyclophosphamide (TAC) on day 5 as preoperative chemotherapy in 28 patients with T2-4 tumors. Effects of oblimersen were evaluated in tumor biopsies and peripheral blood mononuclear cells (PBMCs) 4 days after start of oblimersen and before TAC treatment by quantitative microfluidic real-time PCR. Read-outs consisted in measurement of Bcl-2 mRNA modulations and of 18 putative predictive markers. Two of 13 patients showed a diminution of Bcl-2 transcripts after 4 days of treatment with oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a surrogate tissue because no qualified RNA could be isolated. Nevertheless, we demonstrated feasibility to process clinical samples and to obtain good quality RNA from tumor biopsies and indicated the potential of oblimersen to lower Bcl-2 mRNA in breast cancer.
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PMID:Phase I study of apoptosis gene modulation with oblimersen within preoperative chemotherapy in patients with primary breast cancer. 1960 9

Given that arsenic trioxide (As(2)O(3)) has been successfully used as a chemotherapeutic agent for refractory malignant tumors, this study is aimed at investigating the effect of As(2)O(3) on human Adriamycin resistant osteosarcoma cell line Saos-2. The mechanism underlying multi drug resistance (MDR) in osteosarcoma cells and the anti-tumor effect of As(2)O(3) on Adriamycin resistant osteosarcoma cells were analyzed. In our experiment, we first selected Adriamycin resistant osteosarcoma cell line by growing the classic osteosarcoma cell line Saos-2 in the medium with increasing drug concentrations. Then, we compared the IC50s of the osteosarcoma cells treated with different anticancer drugs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Subsequently, we assessed the expression of classic MDR related molecules, Pgp, multidrug resistance-associated protein (MRP) and glutathione (GSH) activity in the wild type and Adriamycin resistant Saos-2 cells. Furthermore, the apoptosis was assessed by concerning DNA fragment and flow cytometry with Annexin-V staining. To elucidate the underlying mechanism of the apoptosis, related proteins Bcl-2, Bcl-xL, Bax, Bak, cleaved Caspase-3 and cleaved Caspase-9 were analyzed by western blotting. The data showed that the resistance to Adriamycin affected the sensitivity of osteosarcoma cell to other chemotherapeutic agents. The IC50s of Saos-2/ADM cells for methotrexate (1.74-fold), Cisplatin (1.43-fold) and As(2)O(3) (1.21-fold) were increased compared with Saos-2 control cells. The expression of Pgp was upregulated comparing with the control cells. No significant difference was detected about the MRP and the glutathione-S-transferase activity and intracellular GSH concentration among different treated osteosarcoma cells. Apoptosis was observed and proved. The western blotting showed that the expression of Bcl-2 and Bcl-xL was downregulated. Meanwhile, the level of Bax, Bak, cleaved Caspase-3 and cleaved Caspase-9 was upregulated after treated with As(2)O(3). The study suggests that Adriamycin resistant osteosarcoma cells have good response to As(2)O(3)-based chemotherapy in vitro, probably via the pathway of inducing apoptosis. And As(2)O(3) might serve as an excellent alternative candidate for adjuvant chemotherapeutic agent on this incurable pediatric sarcoma.
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PMID:Arsenic trioxide inhibits the growth of adriamycin resistant osteosarcoma cells through inducing apoptosis. 1970 92

This study was designed to investigate the effect and molecular mechanisms of Haishengsu (HSS), a protein extract from a shellfish Tegillarca granosaL., on a drug resistant leukemia cell line. Cultured K562/Adriamycin (ADM) cells were treated with HSS at 10, 20 and 40 microg/mL, respectively. The apoptosis and expression of p-glycoprotein was evaluated by flow cytometry. Expressions of caspase-3 and Bcl-2 were also evaluated. There was a significant dose-dependent increase in the apoptosis in the HSS treated K562/ADM cells (P < 0.05 and 0.01, respectively). The p-glycoprotein expression in the 40 microg/mL HSS group (14.8%) was lower than in the control (16.9%, P < 0.05) and the 10 microg/mL HSS group (7.3%, P < 0.05), but it was similar to the HSS 20 microg/mL group (10.7%, P > 0.05). The expressions of apoptosis-stimulating protein caspase-3 protein were increased, whereas the expressions of apoptosis-suppressing Bcl-2 were decreased in the HSS groups, as compared with the levels in the control group (P < 0.05). We conclude that HSS induces apoptosis of the Adriamycin-resistant K562/ADM cells. The enhanced expressions in caspase-3 and the reduced expressions in Bcl-2 protein may have contributed to the apoptosis-stimulating effect of HSS. The inhibition of p-glycoprotein suggests that HSS may diminish the resistance to Adriamycin and potentially enhance the therapeutic effects.
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PMID:Tegillarca granosa extract Haishengsu inhibits the expression of P-glycoprotein and induces apoptosis in drug-resistant K562/ADM cells. 2064 95

As previously reported, a novel gene P28GANK conferred a multidrug resistant phenotype in gastric cancer cells. The aim of this study was to explore the role of P28GANK in the development of multidrug resistance (MDR) in osteosarcoma cells. P28GANK gene was found to be overexpressed at the mRNA level and the protein level in a cisplatin induced MDR osteosarcoma cell line Saos-2/CDDP compared to its parent cell line Saos-2. Here, we transfected the osteosarcoma cell line Saos-2 with eukaryotic expression vector of P28GANK. In vitro drug sensitivity assay suggested that Saos-2-P28GANK cells conferred resistance to both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs. Blocking P28GANK expression in MDR osteosarcoma cells Saos-2/CDDP by P28GANK-specific small interfering RNA (siRNA) increased the cell sensitivity to various chemotherapeutic drugs. Flow cytometry examination suggested that P28GANK gene expression could suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased release of Adriamycin. Semiquantitative RT-PCR, Western blot and Luciferase reporter assay suggested that P28GANK gene could significantly up-regulate the expression of MDR-1 and Bcl-2, transcription of the MDR-1 gene and down-regulate the expression of Bax. In addition, inhibition of P28GANK expression by RNA interference or P-gp inhibition could partially reverse P28GANK-mediated MDR. Taken together, our findings suggest that down-regulation of P28GANK gene expression could sensitize osteosarcoma cells to chemotherapeutic drugs by down-regulation of the MDR-1 and Bcl-2 and up-regulation of Bax gene expression, without altering the glutathione S-transferase activity, or intracellular glutathione content in osteosarcoma cells. Further study on biological function of P28GANK may be helpful for understanding MDR mechanism of osteosarcoma and developing a strategy for osteosarcoma treatment.
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PMID:Novel gene P28GANK confers multidrug resistance by modulating the expression of MDR-1, Bcl-2 and Bax in osteosarcoma cells. 2128 9

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