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Probiotic?derived ferrichrome inhibits the growth of refractory pancreatic cancer cells.

ABSTRACT: Pancreatic cancer is associated with a poor prognosis due to challenges in early detection, severe progression of the primary tumor, metastatic lesions, and resistance to antitumor agents. However, previous studies have indicated a relationship between the microbiome and pancreatic cancer outcomes. Our previous study demonstrated that ferrichrome derived from Lactobacillus casei, a probiotic bacteria, exhibited tumor?suppressive effects in colorectal and gastric cancer, and that the suppressive effects were stronger than conventional antitumor agents, such as 5?fluorouracil (5?FU) and cisplatin, suggesting that certain probiotics exert antitumorigenic effects. However, whether or not probiotic?derived molecules, including ferrichrome, exert a tumor?suppressive effect in other gastrointestinal tumors, such as pancreatic cancer, remains unclear. In the present study, it was demonstrated that probiotic?derived ferrichrome inhibited the growth of pancreatic cancer cells, and its tumor?suppressive effects were further revealed in 5?FU?resistant pancreatic cancer cells in vitro and in vivo in a mouse xenograft model. Ferrichrome inhibited the progression of cancer cells via dysregulation of the cell cycle by activating p53. DNA fragmentation and cleavage of poly (ADP?ribose) polymerase were induced by ferrichrome treatment, suggesting that ferrichrome induced apoptosis in pancreatic cancer cells. A transcriptome analysis revealed that the expression p53?associated mRNAs was significantly altered by ferrichrome treatment. Thus, the tumor?suppressive effects of probiotics may mediated by probiotic?derived molecules, such as ferrichrome, which may have applications as an antitumor drug, even in refractory and 5?FU?resistant pancreatic cancer.

SUBMITTER: Kita A

PROVIDER: S-EPMC7384844 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Probiotic‑derived ferrichrome inhibits the growth of refractory pancreatic cancer cells.

Kita Akemi A Fujiya Mikihiro M Konishi Hiroaki H Tanaka Hiroki H Kashima Shin S Iwama Takuya T Ijiri Masami M Murakami Yuki Y Takauji Shuhei S Goto Takuma T Sakatani Aki A Ando Katsuyoshi K Ueno Nobuhiro N Ogawa Naoki N Okumura Toshikatsu T

International journal of oncology 20200708 3

Pancreatic cancer is associated with a poor prognosis due to challenges in early detection, severe progression of the primary tumor, metastatic lesions, and resistance to antitumor agents. However, previous studies have indicated a relationship between the microbiome and pancreatic cancer outcomes. Our previous study demonstrated that ferrichrome derived from Lactobacillus casei, a probiotic bacteria, exhibited tumor‑suppressive effects in colorectal and gastric cancer, and that the suppressive ...[more]

PMID: 32705165

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Project description:BackgroundColorectal cancers develop through several pathways, including the adenoma-carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer.MethodsSRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo.ResultsFerrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway.ConclusionsFerrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.

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Probiotic?derived ferrichrome inhibits the growth of refractory pancreatic cancer cells.

Publications

Probiotic‑derived ferrichrome inhibits the growth of refractory pancreatic cancer cells.

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