Dataset Information

Targeting the differentiation of gastric cancer cells (KATO?III) downregulates epithelial?mesenchymal and cancer stem cell markers.

ABSTRACT: The aim of the present study was to analyze the acquisition of the differentiated phenotype in the human gastric signet ring cell adenoma cancer KATO?III cell line in vitro. The morphology of KATO?III cells was explored by microcinematography. Different cytokines secreted by both adherent and non?adherent KATO?III cells into medium were observed. The cancer stem cell phenotypes were identified by reverse transcription?quantitative polymerase chain reaction using primers (E?Cad, Slug, Snail, vimentin, NANOG, NESTIN, OCT3/4 and C?X?C motif chemokine receptor 4) or antibodies [cluster of differentiation (CD)90 and CD117] by flow cytometry (FACS). The influence of the induction media for the differentiation of mesenchymal cells was studied through viability and proliferation assays, by evaluating gene expression and the expression of markers via FACS. Cell viability and cell cycle distribution were evaluated following the treatment of KATO?III with acetyl salicylic acid and using the induction media as an inhibitor of epithelial?mesenchymal transition (EMT) and heparanase. A total of 3 phenotypes of KATO?III were observed (adherent, non?adherent and cell cluster), which have internal potential for cell transition into one of the other phenotypes. KATO?III was differentiated into adipocyte?, chondrocyte?, osteocyte? and neurocyte?like cells by the induction media. Identification of the induced cells was conducted using cell dyes. Reduced mRNA expression of EMT?associated molecules, stem cell markers and heparanase was observed with acetyl salicylic acid and induction media. An inhibitory effect of acetyl salicylic acid and the induction media was also noted in regard to cell proliferation. In addition, acetyl salicylic acid induced G0/G1 phase cell cycle arrest in KATO?III cells. In conclusion, the induction of the differentiation of cancer stem cells into non?proliferating cells offers the possibility for novel drug design to overcome the issues associated with metastasis, drug resistance and systemic toxicity with improved therapeutic efficacy.

SUBMITTER: Shah S

PROVIDER: S-EPMC6609315 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers.

Shah Shahid S Pocard Marc M Mirshahi Massoud M

Oncology reports 20190612 2

The aim of the present study was to analyze the acquisition of the differentiated phenotype in the human gastric signet ring cell adenoma cancer KATO‑III cell line in vitro. The morphology of KATO‑III cells was explored by microcinematography. Different cytokines secreted by both adherent and non‑adherent KATO‑III cells into medium were observed. The cancer stem cell phenotypes were identified by reverse transcription‑quantitative polymerase chain reaction using primers (E‑Cad, Slug, Snail, vime ...[more]

PMID: 31233198

Similar Datasets

Project description:Background and purposeHistone deacetylase (HDAC) inhibitors (HDIs) can modulate the epithelial-mesenchymal transition (EMT) progression and inhibit the migration and invasion of cancer cells. Emerging as a novel class of anti-cancer drugs, HDIs are attracted much attention in the field of drug discovery. This study aimed to discern the underlying mechanisms of Honokiol in preventing the metastatic dissemination of gastric cancer cells by inhibiting HDAC3 activity/expression.Experimental approachClinical pathological analysis was performed to determine the relationship between HDAC3 and tumor progression. The effects of Honokiol on pharmacological characterization, functional, transcriptional activities, organelle structure changes, and molecular signaling were analyzed using binding assays, differential scanning calorimetry, luciferase reporter assay, HDAC3 activity, ER stress response element activity, transmission electron microscopy, immune-blotting, and Wnt/β-catenin activity assays. The in vivo effects of Honokiol on peritoneal dissemination were determined by a mouse model and detected by PET/CT tomography.Key resultsHDAC3 over-expression was correlated with poor prognosis. Honokiol significantly abolished HDAC3 activity (Y298) via inhibition of NFκBp65/CEBPβ signaling, which could be reversed by the over-expression of plasmids of NFκBp65/CEBPβ. Treatments with 4-phenylbutyric acid (a chemical chaperone) and calpain-2 gene silencing inhibited Honokiol-inhibited NFκBp65/CEBPβ activation. Honokiol increased ER stress markers and inhibited EMT-associated epithelial markers, but decreased Wnt/β-catenin activity. Suppression of HDAC3 by both Honokiol and HDAC3 gene silencing decreased cell migration and invasion in vitro and metastasis in vivo.Conclusions and implicationsHonokiol acts by suppressing HDAC3-mediated EMT and metastatic signaling. By prohibiting HDAC3, metastatic dissemination of gastric cancer may be blocked. Conceptual model showing the working hypothesis on the interaction among Honokiol, HDAC3, and ER stress in the peritoneal dissemination of gastric cancer. Honokiol targeting HDAC3 by ER stress cascade and mitigating the peritoneal spread of gastric cancer. Honokiol-induced ER stress-activated calpain activity targeted HDAC3 and blocked Tyr298 phosphorylation, subsequently blocked cooperating with EMT transcription factors and cancer progression. The present study provides evidence to demonstrate that HDAC3 is a positive regulator of EMT and metastatic growth of gastric cancer cells. The findings here imply that overexpressed HDAC3 is a potential therapeutic target for honokiol to reverse EMT and prevent gastric cancer migration, invasion, and metastatic dissemination. • Honokiol significantly abolished HDAC3 activity on catalytic tyrosine 298 residue site. In addition, Honokiol-induced ER stress markedly inhibited HDAC3 expression via inhibition of NFκBp65/CEBPβ signaling. • HDAC3, which is a positive regulator of metastatic gastric cancer cell growth, can be significantly inhibited by Honokiol. • Opportunities for HDAC3 inhibition may be a potential therapeutic target for preventing gastric cancer metastatic dissemination.

Dataset Information

Targeting the differentiation of gastric cancer cells (KATO?III) downregulates epithelial?mesenchymal and cancer stem cell markers.

Publications

Targeting the differentiation of gastric cancer cells (KATO‑III) downregulates epithelial‑mesenchymal and cancer stem cell markers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets