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 herbalist has access to hundreds of years of observational data on the anticancer activity of many herbs. Laboratory studies are expanding the clinical knowledge that is already documented in traditional texts. The herbs that are traditionally used for anti-cancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclo-oxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose-response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as adaptogens, potentially enhancing the efficacy of the conventional therapies or reducing toxicity. Their effectiveness may be increased when multiple agents are used in optimal combinations. New designs for trials to demonstrate activity in human subjects are required. Although controlled trials may be preferable, smaller studies with appropriate endpoints and surrogate markers for anti-angiogenic response could help to prioritize agents for larger, resource-intensive phase iii trials.
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PMID:Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 2. 1757 49

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.
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PMID:Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis. 1767 42

Curcumin, a major pigment of turmeric, is a natural antioxidant possessing a variety of pharmacological activities and therapeutic properties. But its mechanisms are unknown. In our previous study, we found that a 2-h exposure to curcumin induced DNA damage to both the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA) in HepG2 cells and that mtDNA damage was more extensive than nDNA damage. Therefore, experiments were initiated to evaluate the role of mtDNA damage in curcumin-induced apoptosis. The results demonstrated that HepG2 cells challenged with curcumin for 1 h showed a transient elevation of the mitochondrial membrane potential (DeltaPsim), followed by cytochrome c release into the cytosol and disruption of DeltaPsim after 6 h exposure to curcumin. Apoptosis was detected by Hoechst 33342 and annexin V/PI assay after 10 h treatment. Interestingly, the expression of Bcl-2 remained unchanged. A resistance to apoptosis for the corresponding rho0 counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in HepG2 cells mediated by curcumin. The effects of PEG-SOD in protecting against curcumin-induced cytotoxicity suggest that curcumin-induced cytotoxicity is directly dependent on superoxide anion O2- production. These data suggest that mitochondrial hyperpolarization is a prerequisite for curcumin-induced apoptosis and that mtDNA damage is the initial event triggering a chain of events leading to apoptosis in HepG2 cells.
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PMID:Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells. 1769 41

Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited growth of several types of malignant cells both in vivo and in vitro. Its effects on cell proliferation and the induction of apoptosis in human bladder cancer cell lines and intravesical activity in a rat bladder tumor model were studied. Exposure of human bladder cancer cells to curcumin resulted in the induction of apoptotic cell death and caused cells to arrest in the G2/M phase. The anti-apoptotic Bcl-2 and Survivin protein was downregulated by the curcumin treatment together with enhancement of the Bax and p53 expression. The inhibitory activities of curcumin were stronger than those of cisplatin and could not be prevented by catalase pretreatment in T24 cells. Clonal assay indicated large-dose and short-term curcumin was lethal to bladder cancer cells. Moreover, the in vivo study revealed curcumin did induce apoptosis in situ, inhibit and slow the development of bladder cancer. These observations suggest that curcumin could prove an effective chemopreventive and chemotherapy agent for bladder cancer.
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PMID:Effects of curcumin on bladder cancer cells and development of urothelial tumors in a rat bladder carcinogenesis model. 1834 36

Although treatment of Hodgkin's lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signaling cascades, such as NF-kappaB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. Based on the above information, we investigated the capacity of curcumin to inhibit NF-kappaB and STAT3 in H-RS cells, characterizing the functional consequences. Curcumin is incorporated into H-RS cells and acts inhibiting both NF-kappaB and STAT3 activation, leading to a decreased expression of proteins involved in cell proliferation and apoptosis, e.g. Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1, survivin, c-myc and cyclin D1. Interestingly, curcumin caused cell cycle arrest in G2-M and a significant reduction (80-97%) in H-RS cell viability. Furthermore, curcumin triggered cell death by apoptosis, as evidenced by the activation of caspase-3 and caspase-9, changes in nuclear morphology and phosphatidylserine translocation. The above findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with HL.
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PMID:Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells. 1838 90

The antioxidant activity of C.oil in cerebral stroke has been reported earlier. We have attempted here to clarify the mechanisms underlying the neuroprotection against experimental cerebral ischemia by Curcuma oil (C.oil), isolated from the rhizomes of Curcuma longa. C.oil (250 mg/kg i.p.) was given 30 min before focal ischemia in rats caused by occlusion of the middle cerebral artery (1h of occlusion, 24h of reflow). Ischemia, leads to elevation in [Ca(2+)] this sets into motion a cascades of ischemic injury which was attenuated by C.oil. C.oil reduced post-ischemic brain neutrophil infiltration in the ischemic area, controlled tissue NOx levels and the neuronal levels of nitric oxide, peroxynitrite and reactive oxygen species when measured after 24h of reflow. Double immunofluorescence staining analysis and Western immunoblot analysis with C.oil treatment showed that the expression of nitric oxide synthase (NOS) isoforms were decreased significantly compared to the untreated ischemia group. Ischemia is associated with increased in TUNEL (TdT-mediated dUTP nick-end labeling) positive cells in brain sections indicating DNA fragmentation. The C.oil treated group showed a significant decrease in numbers of apoptotic cells compared to the untreated ischemia group, as seen in the flowcytometric analysis of the neurons. Results of immunohistochemistry and Western immunoblot indicate that C.oil suppressed the elevated protein level of Bax, and aided mitochondrial translocation and activation of Bcl-2 by altered mitochondrial membrane potential. It also inhibits the cytosolic release of apoptogenic molecules like cytochrome c, inhibits the activation of caspase-3 and the expression of p53 ultimately inhibiting apoptosis. Our observations suggest that high levels of NO generated by NOS isoforms are partially responsible for exacerbating the neuronal damage induced by MCAo by intraluminal filament.
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PMID:Curcuma oil modulates the nitric oxide system response to cerebral ischemia/reperfusion injury. 1848 79

Furanodiene, a natural product isolated from Curcuma wenyujin, has been reported to produce cytotoxic effect. In this study, we investigated its effects on human leukemia HL60 cells. Furanodiene induced apoptosis of HL60 cells, characterized by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3, caspase-8 and caspase-9. In the Bcl-2 family proteins, Bid protein (a substrate of caspase-8) was activated by furanodiene, but Bcl-2, Bax and Bcl-xL proteins were not influenced by furanodiene stimulation. Moreover, furanodiene treatment caused the upregulation of tumor necrosis factor receptor 1 (TNFR1), the formation of TNFR1 complex and an obvious production of TNF-alpha in HL60 cells. The soluble TNFR1 receptor effectively inhibited furanodiene-induced apoptosis. Taken together, furanodiene could inhibit the growth of leukemia cells via induction of apoptosis, and TNFR1-mediated extrinsic apoptotic pathways explains furanodiene-induced apoptosis.
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PMID:Induction of apoptosis by furanodiene in HL60 leukemia cells through activation of TNFR1 signaling pathway. 1866 67

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

The purpose of this study was to investigate the sensitizing effect of curcumin on cisplatin-induced apoptosis in non-small cell lung cancer (NSCLC) H460 cells. Curcumin was shown to induce superoxide anion generation, down-regulate anti-apoptotic Bcl-2 protein, and subsequently sensitize cells to cisplatin-induced apoptosis. Co-treatment of the cells with curcumin and cisplatin resulted in increased apoptosis and reversal of Bcl-2-mediated cisplatin resistance. The mechanism by which curcumin down-regulates Bcl-2 and sensitizes cells to cisplatin-induced apoptosis involves proteasomal degradation of Bcl-2. These findings indicate a novel pathway for curcumin regulation of Bcl-2, which could benefit the development of a cisplatin sensitizing agent.
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PMID:Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation. 1928 27

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), is extracted from the plant Curcuma longa. It has cytotoxic effects and induces apoptosis in many human cancer cells but the molecular mechanisms are not fully understood. In the present study, we evaluated the effects of curcumin on human breast cancer MDA-MB-231 cells. The cytotoxic effects of curcumin on MDA-MB-231 cells were measured by MTT assay. The percentages of cell cycle were determined by flow cytometry. The protein expressions of p21, 53, Bax and Bcl-2 were examined by Western blotting. The results show that curcumin inhibits the proliferation of MDA-MB-231 cells and induces G2/M arrest in a dose-dependent manner. Curcumin increased the protein expressions of p21 and Bax, but decreased the protein expression of p53 and Bcl-2 in MDA-MB-231 cells. Our results show that one molecular mechanism of curcumin inhibits the proliferation of MDA-MB-231 cells either through up-regulating p21 expression and then inducing apoptosis, or through up-regulating the Bax to Bcl-2 ratio and then inducing apoptosis. Our results also show that curcumin inhibits the migratory activity of MDA-MB-231 cells through down-regulating the protein expression of NF-kappaBp65. Accordingly, the therapeutic potential of curcumin for breast cancer deserves further study.
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PMID:Curcumin inhibits proliferation and migration by increasing the Bax to Bcl-2 ratio and decreasing NF-kappaBp65 expression in breast cancer MDA-MB-231 cells. 1928 22


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