1.Effect of Tiantai No.1 on beta-amyloid-induced neurotoxicity and NF-kappa B and cAMP responsive element-binding protein.
Zheng-zhi WU ; Andrew C J HUANG ; Jean de VELLIS ; Ying-hong LI
Chinese journal of integrative medicine 2008;14(4):286-292
OBJECTIVETo investigate the effect and molecular mechanism of Tiantai No.1, a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by beta-amyloid peptides (Abeta) in vitro and its effects on nuclear factor-kappa B (NF-kappa B) and cAMP responsive element-binding protein (CREB) pathways using the gene transfection technique.
METHODSB104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100, 150, or 200 micro g/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptide1-40 (A beta 1-40, 10 micro mol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (A beta 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 micro g/mL and 150 micro g/mL for 5 days or co-treated with Tiantai No.1 and A beta 1-40 (5 micro mo/L) for 3 days after electroporation for the evaluation of NF-kappa B and CREB expression.
RESULTSPre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (P<0.05, P<0.01). With a dose-dependent relationship, the same treatments increased the expression of NF-kappa B or CREB in B104 neuronal cells (P<0.05, P<0.01). Meanwhile, Tiantai No.1 reduced A beta -40 induced inhibition on NF-kappa B expression (P<0.01).
CONCLUSIONSTiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-kappa B and cAMP cellular signal pathways.
Amyloid beta-Peptides ; Animals ; Apoptosis ; drug effects ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein ; analysis ; Drugs, Chinese Herbal ; pharmacology ; Electroporation ; Luciferases ; Microscopy, Fluorescence ; NF-kappa B ; analysis ; Neurons ; drug effects ; Rats ; Transfection
2.Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity.
Jian HUANG ; Wang LIU ; Bi-Yun LIN ; Jean C LI ; Jane LU ; Ben-Yi LI
Asian Journal of Andrology 2023;25(2):198-207
Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.
Male
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Humans
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Androgens/therapeutic use*
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Receptors, Androgen/genetics*
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Prognosis
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Mitogen-Activated Protein Kinase 8/therapeutic use*
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Cell Line, Tumor
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Prostatic Neoplasms/pathology*
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Prostatic Neoplasms, Castration-Resistant/drug therapy*
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Gene Expression Regulation, Neoplastic