Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.32 (bromelain)
 1,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bromelain is a pharmacologically active compound, present in stems and immature fruits of pineapples (Ananas cosmosus), which has been shown to have anti-edematous, anti-inflammatory, anti-thrombotic and anti-metastatic properties. In the present study, antitumorigenic activity of bromelain was recorded in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted 2-stage mouse skin model. Results showed that bromelain application delayed the onset of tumorigenesis and reduced the cumulative number of tumors, tumor volume and the average number of tumors/mouse. To establish a cause and effect relationship, we targeted the proteins involved in the cell death pathway. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in antiapoptotic protein Bcl-2 in mouse skin. Since persistent induction of cyclooxygenase-2 (Cox-2) is frequently implicated in tumorigenesis and is regulated by nuclear factor-kappa B (NF-kappaB), we also investigated the effect of bromelain on Cox-2 and NF-kappaB expression. Results showed that bromelain application significantly inhibited Cox-2 and inactivated NF-kappaB by blocking phosphorylation and subsequent degradation of IkappaBalpha. In addition, bromelain treatment attenuated DMBA-TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK1/2), mitogen-activated protein kinase (MAPK) and Akt. Taken together, we conclude that bromelain induces apoptosis-related proteins along with inhibition of NF-kappaB-driven Cox-2 expression by blocking the MAPK and Akt/protein kinase B signaling in DMBA-TPA-induced mouse skin tumors, which may account for its anti-tumorigenic effects.
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PMID:Regulation of p53, nuclear factor kappaB and cyclooxygenase-2 expression by bromelain through targeting mitogen-activated protein kinase pathway in mouse skin. 1788 18

Chemoprevention impels the pursuit for either single targeted or cocktail of multi-targeted agents. Bromelain, potential agent in this regard, is a pharmacologically active compound, present in stems and fruits of pineapple (Ananas cosmosus), endowed with anti-inflammatory, anti-invasive and anti-metastatic properties. Herein, we report the anti tumor-initiating effects of bromelain in 2-stage mouse skin tumorigenesis model. Pre-treatment of bromelain resulted in reduction in cumulative number of tumors (CNT) and average number of tumors per mouse. Preventive effect was also comprehended in terms of reduction in tumor volume up to a tune of approximately 65%. Components of the cell signaling pathways, connecting proteins involved in cell death were targeted. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2. A marked inhibition in cyclooxygenase-2 (Cox-2) expression and inactivation of nuclear factor-kappa B (NF-kappaB) was recorded, as phosphorylation and consequent degradation of I kappa B alpha was blocked by bromelain. Also, bromelain treatment curtailed extracellular signal regulated protein kinase (ERK1/2), p38 mitogen-activated protein kinase (MAPK) and Akt activity. The basis of anti tumor-initiating activity of bromelain was revealed by its time dependent reduction in DNA nick formation and increase in percentage prevention. Thus, modulation of inappropriate cell signaling cascades driven by bromelain is a coherent approach in achieving chemoprevention.
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PMID:Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway. 3203 55

The natural anti-cancer agent bromelain is found to be beneficial for either single or multi-targeted therapy in gastric and skin carcinoma, by inhibiting cancer cell growth. Importantly, the presence of peroxidase enhances its biological efficiency. We have now evaluated a panel of cancer cell lines with bromelain in presence or absence of peroxidase to identify that the combination has higher apoptosis inducing potential in all those cell lines. Bromelain plus peroxidase (BM-PR) inhibited acute myeloid (K562) cell proliferation and altered the morphological features. Incidence of apoptosis was established by using annexin V exposure and this was confirmed that the cell cycle was arrested at G0/G1 phase in a concentration-dependent manner. BM-PR increased the intracellular ROS level and altered the mitochondrial membrane potential, as detected using dichlorofluores cin diacetate (DCFDA). It also regulated the expression of apoptosis-related proteins like Bax, Bcl2, caspase-3 and cytochrome besides causing up-regulation of p53 as determined by western blot analysis. These results suggest that BM-PR from pineapple induces apoptosis better than only bromelain in acute myeloid leukemia cells possibly via mitochondria dependent pathway.
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PMID:Bromelain with peroxidase from pineapple are more potent to target leukemia growth inhibition - A comparison with only bromelain. 3045 6

Ferroptosis is a type of regulated cell death dependent on iron and reactive oxygen species. Ferroptosis is distinct from other cell death modalities, including apoptosis, autophagy and necrosis. Dysregulated ferroptosis has been implicated in a number of diseases, including neuropathy, ischemia reperfusion injury, acute kidney failure and cancer. The digestive system consists of several organs. The morbidity and mortality rates of digestive system cancer are high. The current review summarizes the role of ferroptosis in digestive system cancer. A large number of molecules, including tumor protein p53, retinoblastoma protein, nuclear factor E2-related factor 2, KH RNA binding domain containing signal transduction associated 1, cysteine dioxygenase type 1, metallothionein-1G, nuclear receptor coactivator 4, CDGSH iron sulfur domain 1, heat shock protein family A (Hsp70) member 5 and acyl-CoA synthetase long chain family member 4, regulate ferroptosis in digestive system cancer. Drugs such as cisplatin, baicalein, haloperidol, artesunate, piperlongumine, saponin and bromelain may cause cancer cell death by inducing ferroptosis. An improved understanding of ferroptosis in digestive system cancer may give rise to novel diagnostic and making therapeutic strategies.
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PMID:The role of ferroptosis in digestive system cancer. 3140 33