Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have indicated that decursin can induce apoptosis, suppress tumor growth, and inhibit angiogenesis. In this experiment, we investigated how decursin could potentiate the cytotoxic effects of bortezomib in human multiple myeloma cells. We found that decursin inhibited cell viability in U266, MM.1S and ARH77 cells, but not in peripheral blood mononuclear cells (PBMC). Decursin-induced apoptosis through the activation of caspase-8, -9, and -3 in U266 cells. This correlated with the down-regulating of cyclin D1, bcl-2, bcl-xL, survivin, and the vascular endothelial growth factor (VEGF), which are all regulated by the activation of signal transducers and the activator of transcription 3 (STAT3). Indeed, decursin inhibited constitutive STAT3 activation through inhibition of the activation of Janus-activated kinase 2 (JAK2) in U266 cells. In addition, decursin inhibited interleukin-6-inducible STAT3 activation in a time-dependent manner in MM.1S cells. Interestingly, decursin significantly potentiated the apoptotic effects of bortezomib in U266 cells. These effects of decursin were correlated with the suppression of constitutive STAT3 activation in U266 cells. Overall, these results suggest that decursin is a novel blocker of STAT3 activation and it may be a potential candidate for overcoming chemo-resistance through suppression of this signaling.
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PMID:Decursin chemosensitizes human multiple myeloma cells through inhibition of STAT3 signaling pathway. 2112 82

Epidemiological studies have shown that inflammation plays a critical role in the development and progression of various chronic diseases, including cancers, neurological diseases, hepatic fibrosis, diabetic retinopathy, and vascular diseases. Decursin and decursinol angelate (DA) are pyranocoumarin compounds obtained from the roots of Angelica gigas. Several studies have described the anti-inflammatory effects of decursin and DA. Decursin and DA have shown potential anti-inflammatory activity by modulating growth factors such as vascular endothelial growth factor, transcription factors such as signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells, cellular enzymes including matrix metalloproteinases cyclooxygenase, and protein kinases such as extracellular receptor kinase, phosphatidylinositol-3-kinase, and protein kinase C. These compounds have the ability to induce apoptosis by activating pro-apoptotic proteins and the caspase cascade, and reduced the expression of anti-apoptotic proteins such as B-cell lymphoma 2 and B-cell lymphoma-extra-large. Interaction with multiple molecular targets and cytotoxic effects, these two compounds are favorable candidates for treating various chronic inflammatory diseases such as cancers (prostate, breast, leukemia, cervical, and myeloma), rheumatoid arthritis, diabetic retinopathy, hepatic fibrosis, osteoclastogenesis, allergy, and Alzheimer's disease. We have summarized the preliminary studies regarding the biological effects of decursin and DA. In this review, we will also highlight the functions of coumarin compounds that can be translated to a clinical practice for the treatment and prevention of various inflammatory ailments.
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PMID:Decursin and decursinol angelate: molecular mechanism and therapeutic potential in inflammatory diseases. 2913 29