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)

Although Bacillus Calmette-Guerin (BCG) intravesical therapy is a standard treatment for bladder cancer, eventual failure of response is a major problem. Treatments that can augment BCG therapy are urgently needed. We investigated whether curcumin, a component of Curcuma longa (also called turmeric), has potential to improve the current therapy using in vitro and in vivo MBT-2 murine tumor models. We found that curcumin potentiated BCG-induced apoptosis of human bladder cancer cells. BCG stimulated the release of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from peripheral mononuclear neutrophils in a dose- and time-dependent manner, whereas curcumin enhanced the upregulation of TRAIL receptors. Electrophoretic mobility shift assay revealed that curcumin also suppressed the BCG-induced activation of the cell survival transcription factor NF-kappaB. In a syngeneic bladder cancer model, curcumin alone reduced the bladder tumor volume, but a significantly greater reduction was observed when BCG and curcumin were used in combination (P < 0.0001 versus control; P < 0.003 versus BCG alone). This was accompanied by a significant decrease in the proliferation marker Ki-67 (P < 0.01 versus control; P < 0.01 versus BCG alone) and microvessel density (CD31; P < 0.01 versus control; P < 0.01 versus BCG alone), decreased NF-kappaB in tumor tissue compared with the control, induced apoptosis, and decreased cyclin D1, vascular endothelial growth factor, cyclooxygenase-2, c-myc, and Bcl-2 expression in the tumor tissue. Upregulation of TRAIL receptor by the combination was also observed in tumor tissues. Overall, our results suggest that curcumin potentiates the antitumor effect of BCG through the inhibition of NF-kappaB and induction of TRAIL receptors in bladder cancer cells.
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PMID:Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-kappaB and upregulation of TRAIL receptors. 3018 6

In breast cancer, maspin, a serine protease inhibitor, can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. The clinical significance of maspin expression in breast cancer, especially in the sequence of ductal carcinoma in situ (DCIS)-invasive cancer-lymph node metastasis is well known in the Western countries, but its status in the rapidly increasing breast cancers in India remains unknown. The present study was designed to determine the clinical significance of maspin expression in invasive ductal carcinomas of breast (IDCs) in North Indian population and modulation of its expression by curcumin. Immunohistochemical analysis of maspin showed loss or reduced cytoplasmic expression in 36 of 59 (61%) tumors. Furthermore, breast cancer cells (MCF-7 (wild type p53) and MDA-MB-231 (mutant p53)) were treated with curcumin and the effect on expression of maspin gene at transcription and translation levels was analyzed by RT-PCR, immunofluorescence and Western blotting. Maspin expression was also correlated with p53 and Bcl-2 levels. Curcumin inhibited cell growth, induced apoptosis and upregulated maspin gene expression in MCF-7 cells and these findings were further correlated with the upregulation of p53 protein and downregulation of Bcl-2, suggesting maspin mediated apoptosis in MCF-7 cells. To our knowledge this is the first report showing the upregulation of maspin expression by curcumin in breast cancer cells and taken together with the clinical data suggests a potential therapeutic role for curcumin in inducing maspin mediated inhibition of invasion of breast carcinoma cells.
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PMID:Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines. 1994 74

Medulloblastoma is an aggressive primary brain tumor that arises in the cerebellum of children and young adults. The Sonic Hedgehog (Shh) signaling pathway that plays important roles in the pathology of this aggressive disease is a promising therapeutic target. In the present report we have shown that curcumin has cytotoxic effects on medulloblastoma cells. Curcumin suppressed also cell proliferation and triggered cell-cycle arrest at G(2)/M phase. Moreover, curcumin inhibited the Shh-Gli1 signaling pathway by downregulating the Shh protein and its most important downstream targets GLI1 and PTCH1. Furthermore, curcumin reduced the levels of beta-catenin, the activate/phosphorylated form of Akt and NF-kappaB, which led to downregulating the three common key effectors, namely C-myc, N-myc, and Cyclin D1. Consequently, apoptosis was triggered by curcumin through the mitochondrial pathway via downregulation of Bcl-2, a downstream anti-apoptotic effector of the Shh signaling. Importantly, the resistant cells that exhibited no decrease in the levels of Shh and Bcl-2, were sensitized to curcumin by the addition of the Shh antagonist, cyclopamine. Furthermore, we have shown that curcumin enhances the killing efficiency of nontoxic doses of cisplatin and gamma-rays. In addition, we present clear evidence that piperine, an enhancer of curcumin bioavailability in humans, potentiates the apoptotic effect of curcumin against medulloblastoma cells. This effect was mediated through strong downregulation of Bcl-2. These results indicate that curcumin, a natural nontoxic compound, represents great promise as Shh-targeted therapy for medulloblastomas.
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PMID:Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells. 2002 76

Anoikis, an apoptosis triggered by loss of cell anchorage, has been shown to be a principal mechanism of inhibition of tumor metastasis. Recently, anti-apoptotic Bcl-2 and Cav-1 proteins have been demonstrated to be highly associated with tumor metastasis and apoptosis resistance. Curcumin, a major active component of turmeric, Curcuma longa, has been shown to inhibit neoplastic evolution and tumor progression; however, the underlying mechanisms are unclear. In this study, we investigated the effect of curcumin on cell anoikis as a possible mechanism of anti-tumorigenic action of curcumin, and evaluated the potential role of Bcl-2 and Cav-1 in this process. Our results showed that ectopic expression of either Bcl-2 or Cav-1 induced anoikis resistance of lung carcinoma H460 cells. Curcumin downregulated Bcl-2 protein during anoikis and sensitized the cells to detachment-induced apoptosis, whereas it had no significant effect on Cav-1 protein expression. Bcl-2 down-regulation as well as anoikis enhancement by curcumin were inhibited by superoxide anion scavenger, Mn(III)tetrakis(4-benzoic acid) porphyrin chloride, but were unaffected by other ROS scavengers including catalase and deferoxamine, suggesting that superoxide anion is a key player in the downregulation of Bcl-2 by curcumin. Furthermore, we provided evidence that curcumin decreased Bcl-2 level through ubiquitin-proteasomal degradation which sensitized cells to detachment-induced apoptosis. These findings indicate a novel pathway for curcumin regulation of Bcl-2 and provide a key mechanism of anoikis regulation that may be exploited for metastatic cancer treatment.
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PMID:Curcumin sensitizes non-small cell lung cancer cell anoikis through reactive oxygen species-mediated Bcl-2 downregulation. 2012 74

The polyphenol curcumin (diferuloylmethane) is the active componenet of the spice plant Curcuma longa and has been shown to exert multiple actions on mammalian cells. We have studied its effect on folliculostellate (FS) TtT/GF mouse pituitary cells, representative of a multifunctional, endocrine inactive cell type of the anterior pituitary. Proliferation of TtT/GF cells was inhibited by curcumin in a monolayer cell culture and in the colony formation assay in soft agar. Fluorescence-activated cell-sorting (FACS) analysis demonstrated curcumin-induced cell cycle arrest at G(2)/M accompanied by inhibition of cyclin D(1) protein expression. Curcumin had a small effect on necrosis of TtT/GF cells, but it mainly stimulated apoptosis as demonstrated by FACS analysis (Annexin V-fluorescein isothiocyannate/7-aminoactinomycin D staining). Curcumin-induced apoptosis involved suppression of Bcl-2, stimulation of cleaved caspase-3 and induction of DNA fragmentation. Functional studies on FS cell-derived compounds showed that curcumin inhibited mRNA synthesis and release of angiogenic vascular endothelial growth factor-A (VEGF-A). Immune-like functions of FS cells were impaired since curcumin downregulated Toll-like receptor 4, reduced nuclear factor-kappaB expression and suppressed bacterial endotoxin-induced interleukin-6 (IL-6) secretion. The inhibitory action of curcumin on VEGF-A and IL-6 production was also found in primary rat pituitary cell cultures, in which FS cells are the only source of these proteins. The observed effects of curcumin on FS cell growth, apoptosis and functions may have therapeutic consequences for the intrapituitary regulation of hormone production and release as well as for pituitary tumor pathogenesis.
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PMID:Curcumin inhibits the growth, induces apoptosis and modulates the function of pituitary folliculostellate cells. 2016 Apr 30

Curcumin (1), a natural polyphenolic compound, has shown strong antioxidant and anticancer activities. Several molecular mechanisms have been attributed to its inhibitory effects on a wide range of tumor cells. In this study, the response of the chronic myeloid leukemia cell line K562 cells to 1 is investigated. Curcumin inhibited the viability of K562 cells in a dose- and time-dependent manner. Furthermore, curcumin-induced cell death was associated with the formation of the apoptosome complex, the collapse of the mitochondrial membrane potential, and caspase-3 activation. Curcumin treatment also induced Bid cleavage and downregulated the expression of Bcl-2 protein. Surprisingly, even with these molecular features of apoptosis, we showed that 1 stimulated autophagy, which was evidenced by microtubule-associated protein light chain 3 (LC3) immunoreactivty. Curcumin also increased the protein levels of beclin 1 and membrane form LC3 (LC3-II). Autophagy inhibitor bafilomycin A1 and the pan-caspase inhibitor Z-VAD-fmk suppressed curcumin-induced K562 cell death. Overall, these results suggest that curcumin induces autophagic and apoptotic death of K562 cells. These findings suggest that both apoptotic and autophagic mechanisms contribute to the curcumin-induced K562 cell death.
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PMID:Autophagic and apoptotic mechanisms of curcumin-induced death in K562 cells. 2018 54

Medulloblastoma (MB) is the most common malignant brain tumor in children. Bcl-2 and MMP-9 promote the pathogenesis and progression of MB. The expression of both bcl-2 and MMP-9 is regulated by the transcription factor NF-kappaB. Curcumin, a natural food additive, has a potent anti-proliferative effect, presumably mediated through NF-kappaB suppression. The tumor-suppressing effects of curcumin are well documented, however, its effect on MB is unknown. Our objectives were to: a) examine the effect of curcumin on MB cell proliferation and apoptosis; b) characterize the mechanism that mediates the effect of curcumin; c) examine the effects of curcumin on MB cell migration. We report that curcumin inhibited cell proliferation and blocked clonogenicity of MB cells. Furthermore, curcumin down-regulated bcl-2 and bcl(x)l, leading to caspase-mediated cell death. Finally, curcumin blocked migration of MB cells. Thus, we propose developing curcumin as a novel therapeutic agent for MB.
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PMID:Curcumin (diferuloylmethane) induces apoptosis and blocks migration of human medulloblastoma cells. 2033 61

The present study investigated the effect of curcumin, a phenolic compound with yellow color from Curcuma longa L., on the expression of the apoptosis-related genes [BAX (Bcl-2 associated protein X), PKB, p53, MDM2 (mouse double minute 2), caspase 9, c-Ski, smad1 and smad4] in hamster opisthorchiasis. On Opisthorchis viverrini infection treated with dietary curcumin apoptosis-related gene expression profiles were similar to O. viverrini-infected group, but the expression levels seemed lower. Light microscopic observation revealed that aggregation of inflammatory cells surrounding the hepatic bile ducts in the groups infected with O. viverrini and treated with dietary curcumin was lower than in infected group. The intensity of the response is correlated with expression of the genes studied. The results suggest that curcumin reduces pathogenesis in hamster-opisthorchiasis by controlling apoptosis-related gene expression.
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PMID:Effect of curcumin on pathogenesis of hamster-opisthorchiasis through apoptosis-related gene expression. 2057 54

Curcumin has been verified as an anti-cancer compound via multiple molecular targets. Its effective mechanisms include cell cycle arrest, inducing apoptosis, suppressing oncogenes, and enhancing tumor suppressor genes. The resistance of cells to chemotherapy, however, derives from the variable genetic aberration of cancer cells. Consequently, the core signaling pathways of glioblastoma have been explored to evaluate the efficacy of curcumin in proceeding through mutated genes in those pathways. In this study, the efficacy of curcumin was investigated in DBTRG cells. The cytotoxic ability was detected with MTT assay, and the influence of the cell cycle was checked with flow cytometry. The influence of the core signaling pathways was evaluated by Western blotting through the predominantly mutated proteins which included p53, p21, and cdc2 in the p53 pathway, CDKN2A/p16 and RB in the RB pathway, and EGFR, mTOR, Ras, PTEN, and Akt in the RTK-Ras-PI3K pathway. In addition, the apoptotic effect was determined by apoptosis-associated proteins Bcl-2, Bax, and caspase 3. Curcumin exhibits superior cytotoxicity on glioblastoma in a dose- and time-dependent manner in the MTT assay. In the core signaling pathways of glioblastoma, curcumin either significantly influences the p53 pathway by enhancing p53 and p21 and suppressing cdc2 or significantly inhibits the RB pathway by enhancing CDKN2A/p16 and suppressing phosphorylated RB. In the apoptotic pathway, the Bax and caspase 3 are significantly suppressed by curcumin and the Giemsa stain elucidates apoptotic features of DBTRG cells as well. In conclusion, curcumin appears to be an effective anti-glioblastoma drug through inhibition of the two core signaling pathways and promotion of the apoptotic pathway.
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PMID:The anti-cancer efficacy of curcumin scrutinized through core signaling pathways in glioblastoma. 2059 1

The expression of "growth arrest and DNA damage inducible genes 45 and 153" is related to apoptotic induction of cells. GADD45 is an effector gene of the tumor suppressor p53, and GADD153 is associated with cellular function of cancer prevention. Curcumin, isolated from the plant Curcuma longa (LINN), has been investigated as a promising cancer preventive in food because curcumin, a phenolic and coloring compound, is widely ingested in the Indian subcontinent. However, the exact mechanisms of action of curcumin have not yet been clearly elucidated. Based on our successful results with green tea catechins as cancer preventive, we studied the relationship between the expression of GADD45 and 153 and apoptotic induction in human lung cancer cell line PC-9. In our study curcumin increased the expression of GADD45 and 153 in a p53-independent manner. Curcumin also inhibited the growth of PC-9 cells and induced G(1)/S arrest of the cell-cycle followed by strong induction of apoptosis. Treatment with GADD45 and 153 small interfering RNAs (siRNAs) inhibited the apoptotic induction in PC-9 cells by curcumin. Moreover, curcumin induced the expression of cyclin dependent kinase inhibitor genes p21 and p27, while it inhibited the expression of numerous genes, including Bcl-2, cyclin D1, CDK2, CDK4 and CDK6. All the results with PC-9 cells suggest that the up-regulation of GADD45 and 153 by curcumin is a prime mechanism in the anticancer activity of curcumin.
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PMID:Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of "growth arrest and DNA damage inducible genes 45 and 153". 2068 21


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