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Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway.

ABSTRACT: Intake of probiotics or fermented food produced by some probiotic bacteria is believed to exert anti-tumor functions in various cancers, including pancreatic cancer, because several studies have demonstrated the anti-tumor effects of probiotic bacteria in vitro and in vivo in animal carcinogenesis models. However, the mechanisms underlying the anticancer effects of probiotics on pancreatic cancer have not been clarified. In this study, we assessed the anti-tumor effects of probiotic bacteria against pancreatic cancer cells. Among the known probiotic bacteria, Aspergillus oryzae exhibited a strong pancreatic tumor suppression effect. The culture supernatant of A. oryzae was separated by HPLC. Heptelidic acid was identified as an anti-tumor molecule derived from A. oryzae by LC-MS and NMR analysis. The anti-tumor effect of heptelidic acid was exhibited in vitro and in vivo in a xenograft model of pancreatic cancer cells. The anti-tumor effect of heptelidic acid was exerted by the p38 MAPK signaling pathway. Heptelidic acid traverses the intestinal mucosa and exerts anti-tumor effects on pancreatic cancer cells. This is a novel anti-tumor mechanism induced by beneficial bacteria against pancreatic cancer in which bacterial molecules pass through the intestinal tract, reach the extra-intestinal organs, and then induce apoptosis via an inducible signaling pathway.

SUBMITTER: Konishi H

PROVIDER: S-EPMC8154913 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway.

Konishi Hiroaki H Isozaki Shotaro S Kashima Shin S Moriichi Kentaro K Ichikawa Satoshi S Yamamoto Kazuki K Yamamura Chikage C Ando Katsuyoshi K Ueno Nobuhiro N Akutsu Hiroaki H Ogawa Naoki N Fujiya Mikihiro M

Scientific reports 20210526 1

Intake of probiotics or fermented food produced by some probiotic bacteria is believed to exert anti-tumor functions in various cancers, including pancreatic cancer, because several studies have demonstrated the anti-tumor effects of probiotic bacteria in vitro and in vivo in animal carcinogenesis models. However, the mechanisms underlying the anticancer effects of probiotics on pancreatic cancer have not been clarified. In this study, we assessed the anti-tumor effects of probiotic bacteria aga ...[more]

PMID: 34040123

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Project description:BackgroundGlycosylation is crucial for the stability and biological functions of proteins. The aberrant glycosylation of critical proteins plays an important role in multiple cancers, including lung adenocarcinoma (LUAD). STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A) is a major isoform of N-linked glycosyltransferase that catalyzes the glycosylation of various proteins. However, the functions of STT3A in LUAD are still unclear.MethodsThe expression profiles of STT3A were initially analyzed in public data sets and then validated by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry assays in clinical LUAD samples. The overall survival (OS) between patients with high and low STT3A expression was compared using a Kaplan-Meier curve with a log-rank analysis. STT3A was knocked-out using CRISPR/Cas9 and inhibited by NGI-1. Cell Counting Kit-8, colony formation assay, wound-healing, transwell assay, and flow cytometry were performed to assess the cellular functions of STT3A in vitro. A mice xenograft model was established to investigate the effects of STT3A on tumor growth in vivo. Further, the downstream signaling pathways of STT3A were screened by mass spectrometry with a bioinformatics analysis, and the activation of the target pathways were subsequently validated by Western blot.ResultsThe expression of STT3A was frequently upregulated in LUAD tissues than normal lung tissues. The high expression of STT3A was significantly associated with poor OS in LUAD patients. The knockout or inhibition of STT3A suppressed proliferation, migration, and invasion, and arrested the cell cycle of LUAD cell lines in vitro. Similarly, the knockout or inhibition of STT3A suppressed tumor growth in vivo. In terms of molecular mechanism, STT3A may promote LUAD progression by activating the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT) pathways and regulating the epithelial-mesenchymal transition.ConclusionsSTT3A promotes LUAD progression via the MAPK and PI3K/AKT signaling pathways and could serve as a novel prognostic biomarker and potential therapeutic target for LUAD patients.

Dataset Information

Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway.

Publications

Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway.

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