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 carcino...

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Autores principales:	Hiroaki Konishi, Shotaro Isozaki, Shin Kashima, Kentaro Moriichi, Satoshi Ichikawa, Kazuki Yamamoto, Chikage Yamamura, Katsuyoshi Ando, Nobuhiro Ueno, Hiroaki Akutsu, Naoki Ogawa, Mikihiro Fujiya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cfb8f92149174db3bf6dd9dbd49d3505
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spelling	oai:doaj.org-article:cfb8f92149174db3bf6dd9dbd49d35052021-12-02T16:53:18ZProbiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway10.1038/s41598-021-90707-42045-2322https://doaj.org/article/cfb8f92149174db3bf6dd9dbd49d35052021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90707-4https://doaj.org/toc/2045-2322Abstract 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.Hiroaki KonishiShotaro IsozakiShin KashimaKentaro MoriichiSatoshi IchikawaKazuki YamamotoChikage YamamuraKatsuyoshi AndoNobuhiro UenoHiroaki AkutsuNaoki OgawaMikihiro FujiyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiroaki Konishi Shotaro Isozaki Shin Kashima Kentaro Moriichi Satoshi Ichikawa Kazuki Yamamoto Chikage Yamamura Katsuyoshi Ando Nobuhiro Ueno Hiroaki Akutsu Naoki Ogawa Mikihiro Fujiya Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway
description	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.
format	article
author	Hiroaki Konishi Shotaro Isozaki Shin Kashima Kentaro Moriichi Satoshi Ichikawa Kazuki Yamamoto Chikage Yamamura Katsuyoshi Ando Nobuhiro Ueno Hiroaki Akutsu Naoki Ogawa Mikihiro Fujiya
author_facet	Hiroaki Konishi Shotaro Isozaki Shin Kashima Kentaro Moriichi Satoshi Ichikawa Kazuki Yamamoto Chikage Yamamura Katsuyoshi Ando Nobuhiro Ueno Hiroaki Akutsu Naoki Ogawa Mikihiro Fujiya
author_sort	Hiroaki Konishi
title	Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway
title_short	Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway
title_full	Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway
title_fullStr	Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway
title_full_unstemmed	Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathway
title_sort	probiotic aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 mapk signaling pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cfb8f92149174db3bf6dd9dbd49d3505
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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

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