The compounds are also relatively poor hexosaminidase substrates and thus provide useful alternatives to 4'-deoxychitobiosyl-4-methylumbelliferone, previously reported by us as fluorogenic substrate to monitor CHIT1 activity as a marker for Gaucher disease state
As shown in , in PC3-ML and LAPC-4 cells, 4-MU induced activation of pro-apoptotic effectors, caspase-8, caspase-9 and caspase-3 (2–4 fold) and PARP cleavage. shows that 4-MU induced up-regulation of Fas-L, Fas, FADD and DR4 and bid cleavage (p15bid); at 0.4 mM concentration there was 1.8–3-fold up-regulation of these death-inducing signaling complex (DISC) proteins. Eight hours following 4-MU treatment there was up-regulation of Fas-L, Fas and DR4, with a maximal increase occurring by 12 h (). 4-MU also caused a decrease in bcl-2 (> 4-fold), bcl-XL ( 2-fold) levels. Addition of HA during 4-MU treatment, prevented the up- or down-regulation of each of the signaling molecules in the apoptosis cascade ().These results show that 4-MU decreased cell survival mainly by inducing the extrinsic pathway of apoptosis.
Synthesis and Properties of 4-Methyl-2-oxo-1,2 …
Posey JT, Soloway MS, Ekici S, Sofer M,Civantos F, Duncan RC and Lokeshwar VB: Evaluation of prognosticpotential of hyaluronic acid and hyaluronidase (HYAL1) for prostatecancer. Cancer Res. 63:2638–2644. 2003.
Design and synthesis of antimicrobial, anticoagulant, …
Analyses of tumor tissue extracts from the experiment described in showed increased levels of activated caspase-8, caspase-9, caspase-3, cleaved PARP and DR4 and decreased levels of CD44, RHAMM, HAS2 and caveolin-1 in tumor extracts from 4-MU treated animals. This suggests that 4-MU reduces tumor growth by increasing apoptosis and decreasing the expression of HA receptors and related molecules.
Formal Lab Report-Carbethoxycoumarin | Hydrogen | Ester
We next determined whether 4-MU delayed tumor growth if the treatment started after the tumors become palpable (7th day). As shown in , 4-MU (450 mg/kg) significantly slowed tumor growth (P
To Formal Lab Report-Carbethoxycoumarin.
Effect of 4-MU treatment by oral gavage on PC3-ML xenografts is shown in . 4-MU significantly inhibited tumor growth at both, 225 mg/kg and 450 mg/kg, doses (P ), the 4-MU treatment (450 mg/kg) did not cause such reductions (P > 0.05 ). 4-MU also did not cause gross histological changes in prostate, testis, seminal vesicles, liver, kidney and lung tissues (data not shown). Serum chemistry analysis showed no significant differences in blood urea nitrogen, creatinine, SGPT, and alkaline phosphatase levels from vehicle and 4-MU treated (450 mg/kg) animals (P > 0.05; ); blood clotting time is also similar in both groups.
ANTITUMOR ACTIVITY OF HYALURONIC ACID SYNTHESIS …
To understand the mechanism by which 4-MU might inhibit cell growth, gene expression and induce apoptosis, we evaluated various effects of 4-MU in PC3-ML cells transfected with a myristoylated-Akt plasmid (m-Akt, constitutively active Akt). As shown in , m-Akt transfection increased total Akt levels by 3-fold and p-Akt levels by over 10-fold when compared to the vector control. p-Akt levels were not appreciably reduced ( show that m-Akt expression attenuated the effect of 4-MU on cell growth, apoptosis and NFkB reporter activity. Expression of myr-Akt also reversed the inhibitory effect of 4-MU on IL-8, HAS2, RHAMM, CD44 and MMP-9 expression (). However, myr-Akt expression did not alter the 4-MU induced down regulation of Caveolin-1, CXCR1, CXCR7, and CXCR4 mRNAs (data not shown).