The Maillard reaction products are known to be effective in chemoprevention. Here, we focused on the anti-cancer effects of (
E
)-2,4-bis(
p
-hydroxyphenyl)-2-butenal on in vitro and in vivo colon ...cancer. We analysed the anti-cancer activity of (
E
)-2,4-bis(
p
-hydroxyphenyl)-2-butenal on colon cancer cells by using cell cycle and apoptosis analysis. To elucidate it’s mechanism, NF-κB DNA binding activity, docking model as well as pull-down assay. Further, a xenograft model of colon cancer was studied to test the in vivo effects of (
E
)-2,4-bis(
p
-hydroxyphenyl)-2-butenal. (
E
)-2,4-Bis(
p
-hydroxyphenyl)-2-butenal inhibited colon cancer cells (SW620 and HCT116) growth followed by induction of apoptosis in a concentration-dependent manner via down-regulation of NF-κB activity. In docking model as well as pull-down assay, (
E
)-2,4-bis(
p
-hydroxyphenyl)-2-butenal directly binds to three amino acid residues of IKKβ, thereby inhibited IKKβ activity in addition to induction of death receptor 6 (DR6) as well as their target apoptotic genes. Finally, (
E
)-2,4-bis(
p
-hydroxyphenyl)-2-butenal suppressed anchorage-independent cancer cell growth, and tumor growth in xenograft model accompanied with apoptosis through inhibition of IKKβ/NF-κB activity, and overexpression of DR6. These results suggest that (
E
)-2,4-bis(
p
-hydroxyphenyl)-2-butenal inhibits colon cancer cell growth through inhibition of IKKβ/NF-κB activity and induction of DR6 expression.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and Purpose
Products of Maillard reactions between aminoacids and reducing sugars are known to have anti‐inflammatory properties. Here we have assessed the anti‐arthritis effects of ...(E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal and its possible mechanisms of action.
Experimental Approach
We used cultures of LPS‐activated macrophages (RAW264.7 cells) and human synoviocytes from patients with rheumatoid arthritis for in vitro assays and the collagen‐induced arthritis model in mice. NO generation, iNOS and COX2 expression, and NF‐κB/IKK and STAT3 activities were measured in vitro and in joint tissues of arthritic mice, along with clinical scores and histopathological assessments. Binding of (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal to STAT3 was evaluated by a pull‐down assay and its binding site was predicted using molecular docking studies with Autodock VINA.
Key Results
(E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal (2.5–10 μg·mL−1) inhibited LPS‐inducedNO generation, iNOS and COX2 expression, and NF‐κB/IKK and STAT3 activities in macrophage and human synoviocytes. This compound also suppressedcollagen‐induced arthritic responses in mice by inhibiting expression of iNOS and COX2, and NF‐κB/IKK and STAT3 activities; it also reduced bone destruction and fibrosis in joint tissues. A pull‐down assay showed that (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal interfered with binding of ATP to STAT3. Docking studies suggested that (E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal bound to the DNA‐binding interface of STAT3 possibly inhibiting ATP binding to STAT3 in an allosteric manner.
Conclusions and Implications
(E)‐2,4‐bis(p‐hydroxyphenyl)‐2‐butenal exerted anti‐inflammatory and anti‐arthritic effects through inhibition of the NF‐κB/STAT3 pathway by direct binding to STAT3. This compound could be a useful agent for the treatment of arthritic disease.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
2,4-Bis(p-hydroxyphenyl)-2-butenal (Butenal), a tyrosine-fructose Maillard reaction product has been demonstrated as an effective compound for prevention of neuroinflammatory diseases. However, this ...compound was vulnerable to environmental factors. Our research has been continuously made to improve druggability of Butenal and identified 2,4-bis(4-hydroxyphenyl)but-2-enal diacetate (HPBD) as an alternative. Herein, to investigate potential anti-neuroinflammatory and anti-amyloidogenic effects of HPBD, we treated HPBD (0.5, 1, and 2 μg/ml) on the lipopolysaccharides (LPS) (1 μg/ml) stimulated astrocytes and microglial BV-2 cell. HPBD inhibited LPS-induced NO and ROS production, and LPS-elevated expression of iNOS, COX2, β-site APP-cleaving enzyme 1 (BACE1), C99, and Aβ1–42 levels as well as attenuation of β-secretase activities. The activation of nuclear factor-kappaB (NF-κB), signal transducer and activator of transcription1 (STAT1), and STAT3 was concomitantly inhibited by HPBD. Moreover, siRNA targeting STAT3 abolished HPBD-induced inhibitory effects on neuro-inflammation and amyloidogenesis. In addition, pull down assay and docking model showed interaction of HPBD with STAT3. These findings suggest that HPBD may be useful and potentially therapeutic choices for the treatment of neuroinflammatory diseases.
•We used glia cells to identify neuroinflammation effects of HPBD.•HPBD prevents LPS-induced inflammatory response and amyloidogenesis.•The inhibition of STATs attenuates the inactivation of NF-κB by HPBD.•The interaction of HPBD with STAT3 controls neuroinflammation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
(
)-2-Methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP), derived from butenal, is a recently synthesized Maillard reaction product. Owing to its novelty, little is known about the function ...of MMPP. In this study, we elucidated the effects of MMPP on apoptosis in cervical cancer by using the HeLa cervical cancer cell line, which is widely used in cancer research. We observed that MMPP was cytotoxic to HeLa cells and induced activation of caspase-3, -8, and -9, without affecting the expression of the viral oncogenes
and
. In particular, the expression of the death receptors DR5 and FAS was significantly increased by MMPP treatment. There were no significant alterations of mitochondrial intrinsic factors. Taking all these results together, our findings show that MMPP primarily induces apoptosis in HeLa cervical cancer cells via the extrinsic apoptotic signaling pathway, accompanied by an enhanced expression of death receptors.
Activation of nuclear factor kappa-B (NF-κB) is implicated in drug resistant of lung cancer cells. Our previous data showed that thiacremonone inhibited activation of NF-κB. In the present study, we ...investigated whether thiacremonone enhanced susceptibility of lung cancer cells to a common anti-cancer drug paclitaxel by further inhibition of NF-κB. Thus, we used the threefold lower doses of IC₅₀ values (50 μg/ml thiacremonone and 2.5 nM paclitaxel). We found that combination treatment with thiacremonone and paclitaxel was more susceptible (combination index; 0.40 in NCI-H460 cells and 0.46 in A549 cells) in cell growth inhibition of two types of lung cancer cell lines compared to a single agent treatment. Consistent with the combination effect on cancer cell growth inhibition, the combination treatment further induced apoptotic cell death and arrested the cancer cells in G2/M phase accompanied with a much lower expression of cdc2 and cyclin B1, and inhibited colony formation. Much more inactivation of NF-κB and greater expression of NF-κB target apoptosis regulated genes such as caspase-8 and PARPs were found by the combination treatment. Molecular model and pull down assay as well as MALDI-TOF analysis demonstrated that thiacremonone directly binds to p50. These data indicated that thiacremonone leads to increased apoptotic cell death in lung cancer cell lines through greater inhibition of NF-κB by the combination treatment with paclitaxel.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Maillard reaction products are known to be effective in chemoprevention. Here, we focused on the anti-cancer effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on in vitro and in vivo colon ...cancer. We analysed the anti-cancer activity of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on colon cancer cells by using cell cycle and apoptosis analysis. To elucidate it's mechanism, NF-kappaB DNA binding activity, docking model as well as pull-down assay. Further, a xenograft model of colon cancer was studied to test the in vivo effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibited colon cancer cells (SW620 and HCT116) growth followed by induction of apoptosis in a concentration-dependent manner via down-regulation of NF-kappaB activity. In docking model as well as pull-down assay, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal directly binds to three amino acid residues of IKKbeta, thereby inhibited IKKbeta activity in addition to induction of death receptor 6 (DR6) as well as their target apoptotic genes. Finally, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed anchorage-independent cancer cell growth, and tumor growth in xenograft model accompanied with apoptosis through inhibition of IKKbeta/NF-kappaB activity, and overexpression of DR6. These results suggest that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal inhibits colon cancer cell growth through inhibition of IKKbeta/NF-kappaB activity and induction of DR6 expression.PUBLICATION ABSTRACT
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this paper, the simplified approach using commercial computer software code was adopted to predict the performance of a kettle typed shell and tube heat exchanger. Similarly the numerical analysis ...using ANSYS/CFX is conducted for the same design and the result data are collected to analyze its performance numerically. In general, the heat exchanger performances are evaluated by predicting the temperature difference and pressure drop. The result data of both the analysis are compared to find the differences between the data. From the comparison, we came to know that the error percentage between the two analysis results is very low which is acceptable proving our design is convincible. Thereby we fabricated a prototype model of shell and tube heat exchanger (kettle type) with the same parameters used for these analyses.
PDF
