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Identification of a novel biomarker in tangeretin?induced cell death in AGS human gastric cancer cells.

ABSTRACT: Proteomic analysis serves as an important biological tool for identifying biological events. Novel biomarkers of a specific disease such as cancer may be identified using these promising techniques. The aim of the present study was to investigate the effect of tangeretin and to identify potential biomarkers in AGS gastric cancer cells using a proteomics approach. The results of the present study revealed that tangeretin inhibited AGS cell viability dose?dependently with a half?maximal inhibitory concentration of 100 µM. Two?dimensional gel electrophoresis was performed to determine the potential biomarker between control and tangeretin (100 µM)?treated AGS cells. A total of 16 proteins was identified from 36 significant protein spots using matrix?assisted laser?desorption/ionization time?of?flight?mass spectrometry using peptide fingerprinting. The bioinformatics tools Protein ANalysis THrough Evolutionary Relationships (PANTHER) and Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to identify the functional properties and association of the proteins obtained. Using western blot analysis, the regulatory pattern of four selected proteins, protein kinase C?, mitogen?activated protein kinase 4, phosphoinositide 4?kinase and poly(ADP?ribose) polymerase 14, were successfully verified in replicate sample sets. These selected proteins are primarily involved in apoptosis signaling, angiogenesis, cell cycle regulation, receptor kinase binding, intracellular cytoplasmic and nuclear alterations. Therefore, aim of the present study was to identify potential diagnostic biomarkers from the functional categories of altered protein expression in tangeretin?inhibited AGS gastric cancer cell viability.

SUBMITTER: Yumnam S

PROVIDER: S-EPMC6196609 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Identification of a novel biomarker in tangeretin‑induced cell death in AGS human gastric cancer cells.

Yumnam Silvia S Raha Suchismita S Kim Seong Min SM Venkatarame Gowda Saralamma Venu V Lee Ho Jeong HJ Ha Sang Eun SE Heo Jeong Doo JD Lee Sang Joon SJ Kim Eun Hee EH Lee Won Sup WS Kim Jin A JA Kim Gon Sup GS

Oncology reports 20180924 6

Proteomic analysis serves as an important biological tool for identifying biological events. Novel biomarkers of a specific disease such as cancer may be identified using these promising techniques. The aim of the present study was to investigate the effect of tangeretin and to identify potential biomarkers in AGS gastric cancer cells using a proteomics approach. The results of the present study revealed that tangeretin inhibited AGS cell viability dose‑dependently with a half‑maximal inhibitory ...[more]

PMID: 30272339

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Project description:We recently discovered a novel nargenicin A1 analog, 23-demethyl 8,13-deoxynargenicin (compound 9), with potential anti-cancer and anti-angiogenic activities against human gastric adenocarcinoma (AGS) cells. To identify the key molecular targets of compound 9, that are responsible for its biological activities, the changes in proteome expression in AGS cells following compound 9 treatment were analyzed using two-dimensional gel electrophoresis (2-DE), followed by MALDI/TOF/MS. Analyses using chemical proteomics and western blotting revealed that compound 9 treatment significantly suppressed the expression of cyclophilin A (CypA), a member of the immunophilin family. Furthermore, compound 9 downregulated CD147-mediated mitogen-activated protein kinase (MAPK) signaling pathway, including c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) by inhibiting the expression of CD147, the cellular receptor of CypA. Notably, the responses of AGS cells to CypA knockdown were significantly correlated with the anticancer and antiangiogenic effects of compound 9. CypA siRNAs reduced the expression of CD147 and phosphorylation of JNK and ERK1/2. In addition, the suppressive effects of CypA siRNAs on proliferation, migration, invasion, and angiogenesis induction of AGS cells were associated with G2/M cell cycle arrest, caspase-mediated apoptosis, inhibition of MMP-9 and MMP-2 expression, inactivation of PI3K/AKT/mTOR pathway, and inhibition of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. The specific interaction between compound 9 and CypA was also confirmed using the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA) approaches. Moreover, in silico docking analysis revealed that the structure of compound 9 was a good fit for the cyclosporin A binding cavity of CypA. Collectively, these findings provide a novel molecular basis for compound 9-mediated suppression of gastric cancer progression through the targeting of CypA.

Dataset Information

Identification of a novel biomarker in tangeretin?induced cell death in AGS human gastric cancer cells.

Publications

Identification of a novel biomarker in tangeretin‑induced cell death in AGS human gastric cancer cells.

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