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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-90707-4 |
| _version_ | 1818433262175911936 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T16:18:18Z |
| format | Article |
| id | doaj.art-cfb8f92149174db3bf6dd9dbd49d3505 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T16:18:18Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cfb8f92149174db3bf6dd9dbd49d35052022-12-21T22:54:52ZengNature PortfolioScientific Reports2045-23222021-05-0111111210.1038/s41598-021-90707-4Probiotic Aspergillus oryzae produces anti-tumor mediator and exerts anti-tumor effects in pancreatic cancer through the p38 MAPK signaling pathwayHiroaki Konishi0Shotaro Isozaki1Shin Kashima2Kentaro Moriichi3Satoshi Ichikawa4Kazuki Yamamoto5Chikage Yamamura6Katsuyoshi Ando7Nobuhiro Ueno8Hiroaki Akutsu9Naoki Ogawa10Mikihiro Fujiya11Department of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical UniversityDivision of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityFaculty of Pharmaceutical Science, Hokkaido UniversityFaculty of Pharmaceutical Science, Hokkaido UniversityDivision of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityDivision of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical UniversityCenter for Advanced Research and Education, Asahikawa Medical UniversityCenter for Advanced Research and Education, Asahikawa Medical UniversityDepartment of Gastroenterology and Advanced Medical Sciences, Asahikawa Medical UniversityAbstract 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.https://doi.org/10.1038/s41598-021-90707-4 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-90707-4 |
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