PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is an aggressive solid tumour characterised by few early symptoms, high mortality, and lack of effective treatment. Therefore, it is important to identify new potential therapeutic targets and prognostic biomarkers of PAAD. METHODS: The Cancer Genome Atlas and Genotype-Tissue Expression databases were used to identify the expression and prognostic model of protocadherin 1 (PCDH1). The prognostic performance of risk factors and diagnosis of patients with PAAD were evaluated by regression analysis, nomogram, and receiver operating characteristic curve. Paraffin sections were collected from patients for immunohistochemistry (IHC) analysis. The expression of PCDH1 in cells obtained from primary tumours or metastatic biopsies was identified using single-cell RNA sequencing (scRNA-seq). Real-time quantitative polymerase chain reaction (qPCR) and western blotting were used to verify PCDH1 expression levels and the inhibitory effects of the compounds. RESULTS: The RNA and protein levels of PCDH1 were significantly higher in PAAD cells than in normal pancreatic ductal cells, similar to those observed in tissue sections from patients with PAAD. Aberrant methylation of the CpG site cg19767205 and micro-RNA (miRNA) hsa-miR-124-1 may be important reasons for the high PCDH1 expression in PAAD. Up-regulated PCDH1 promotes pancreatic cancer cell metastasis. The RNA levels of PCDH1 were significantly down-regulated following flutamide treatment. Flutamide reduced the percentage of PCDH1 RNA level in PAAD cells Panc-0813 to < 50%. In addition, the PCDH1 protein was significantly down-regulated after Panc-0813 cells were incubated with 20 µM flutamide and proves to be a potential therapeutic intervention for PAAD. CONCLUSION: PCDH1 is a key prognostic biomarker and promoter of PAAD metastasis. Additionally, flutamide may serve as a novel compound that down-regulates PCDH1 expression as a potential treatment for combating PAAD progression and metastasis.

Isolation of a new monoterpenoid glycoside from Anhua dark tea based on an NMR-guided method and its cytotoxic activity against MDA-MB-231 and SH-SY5Y cell lines.

Based on an NMR-guided method, one new monoterpenoid glycoside (1) was isolated from Anhua dark tea, together with five known compounds (2-6). The structure of the new compound was determined as 3-(5,5-dimethyltetrahydrofuranyl)-1-buten-3-ol primeveroside, and trivially named anhuaterpenoside A (1), on the basis of detailed spectroscopic analyses, and acidic hydrolysis. Compound 1 exhibits cytotoxic activity against MDA-MB-231 and SH-SY5Y cell lines with IC50 value of 23.26 µM and 18.57 µM, respectively.

Neuroprotective effect of catechins derivatives isolated from Anhua dark tea on NMDA-induced excitotoxicity in SH-SY5Y cells.

Anhua dark tea known as the earliest produced Chinese dark tea, has been commercially available and famous for its unique flavor and health care effect. NMDA receptors are glutamate-coupled ion channels that critically involved in survival of neuronal cells and neurodegenerative diseases. Thus, it is considered a promising target for the therapy of neurodegenerative disease. In this study, four catechins including two new catechins derivatives (1-2), together with thirteen known flavonoids were isolated from Anhua dark tea. The structures of compounds 1-2 [2S,3R-6-methoxycarbonylgallocatechin (1) and 2R,3R-6-methoxycarbonylgallocatechin (2)] were determined on the basis of their spectroscopic data. The preliminary bioassay indicated that compound 1 showed the best neuroprotective effects via N-methyl-d-aspartate (NMDA) receptors inhibition. Compound 1 protected SH-SY5Y cells against NMDA-induced injury and cell apoptosis via the modulation of NR2B expression, the activation of PI3K/Akt signaling and caspase-dependent pathway. The results suggested compound 1 would be a potent dietary therapy reagent for prevention of excitable brain injury.