Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Betulinic acid (BA) is a pentacyclic triterpene found in a number of medicinal plants and has been shown to cause apoptosis in a number of cell lines. We report here that BA may also have an effect on HL-60 cell differentiation. BA was cytotoxic to HL-60 cells with an IC50 of 5.7 microM after a 72-h treatment. Flow cytometry analysis showed that after exposure to 1-12 microM of BA for 72 h, approximately 10% of viable cells were in the sub-G1, presumably apoptotic, phase. At the same time differentiation was induced in approximately 10% (at 1 microM BA) to a maximum of 20% (at 6 microM BA) of cells as judged by the NBT-reduction test, and the expression of membrane markers CD11b and CD14. On the other hand, at 1 and 5 nM, 1alpha,25-dihydroxyvitamin D3 (DHD3) induced differentiation in approximately 10 and 70% of cells, respectively. At 1 nM DHD3, the addition of 1 microM BA increased differentiated cells from 10 to 43% and with 3 microM BA the increase was to 80%. BA also enhanced the effects of DHD3 in the expansion of the G1 cell population with a concomitant decrease of S phase cells. The effects of DHD3 and BA on CD11b and CD14 expression were inhibited by PD98059, a MEK inhibitor. Our results suggest that BA may enhance the effect of DHD3 in inducing mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase-mediated HL-60 cell differentiation.
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PMID:Betulinic acid enhances 1alpha,25-dihydroxyvitamin D3-induced differentiation in human HL-60 promyelocytic leukemia cells. 1520 7

Previously, betulinic acid was identified as one of the main compounds responsible for the anti-melanogenic effect in Vitis amurensis root. In this study, we investigated the precise mechanism underlying the anti-melanogenic activity of betulinic acid in B16F10 cells. Betulinic acid significantly attenuated 3-isobutyl-1-methylxanthine (IBMX)-induced melanin production by inhibiting tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 expression through the modulation of their corresponding transcription factors, microphthalamia associated transcription factor (MITF) and cAMP response element binding protein (CREB), in B16F10 cells. In addition, phosphorylation of mitogen-activated protein kinase kinase (MEK)/extracellular regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/Akt, involved in the melanogenic processes, were ameliorated by betulinic acid treatment. Role of MEK/ERK and PI3K/Akt signaling pathway in the melanogenesis was confirmed by using specific inhibitors, PD98059 (for MEK/ERK) and LY294002 (for PI3K/Akt), respectively. As a result, betulinic acid inhibited melanin production by tyrosinase, TRP-1, and TRP-2 inhibition through the regulation of CREB and MITF, which was accompanied with MEK/ERK and PI3K/Akt inactivation in IBMX-stimulated B16F10 cells. Consequently, these results demonstrate a novel molecular function of betulinic acid derived from V. amurensis root in melanogenesis, which in turn enhances our understanding on the application of cosmetic therapy for reducing skin hyperpigmentation.
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PMID:Betulinic acid isolated from Vitis amurensis root inhibits 3-isobutyl-1-methylxanthine induced melanogenesis via the regulation of MEK/ERK and PI3K/Akt pathways in B16F10 cells. 2463 67