Probiotic Aspergillus Oryzae Produces Anti-tumor Mediator and Exerts Anti-tumor Effects in Pancreatic Cancer Through the P38 MAPK Signaling Pathway

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 27

PMID 34040123

Citations 11

Authors

Hiroaki Konishi

Shotaro Isozaki

Shin Kashima

Kentaro Moriichi

Satoshi Ichikawa

Kazuki Yamamoto

Chikage Yamamura

Katsuyoshi Ando

Nobuhiro Ueno

Hiroaki Akutsu

Naoki Ogawa

Mikihiro Fujiya

Affiliations

Soon will be listed here.

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.

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