Anti-tumor effect of a recombinant Bifidobacterium strain secreting a claudin-targeting molecule in a mouse breast cancer model
Abstract
Bifidobacterium is a nonpathogenic strain of anaerobic bacteria that selectively localizes and proliferates in tumors. It has emerged as a specific carrier of anticancer proteins against malignant tumors. Claudins are tetraspanin transmembrane proteins that form tight junctions. Claudin-4 is overexpressed in certain epithelial malignant cancers. The C-terminal fragment of the Clostridium perfringens enterotoxin (C-CPE), an exotoxin without the cytotoxic domain, strongly binds to claudin-4. The C-CPE fusion toxin (C-CPE-PE23), which targets claudin-4, strongly suppresses tumor growth; however, C-CPE fusion toxins exhibit hepatic toxicity. In this study, we successfully generated a strain of Bifidobacterium longum that secreted C-CPE-PE23 (B. longum-C-CPE-PE23) and was specific to and cross reactive with human and mouse claudin-4. We evaluated the therapeutic potential of this strain against triple-negative breast cancer using a mouse model. C-CPE-PE23 decreased cell viability in a dose-dependent manner in human and mouse breast cancer cell lines. After intravenous injection, Bifidobacterium was specifically distributed in the tumors of mice bearing breast cancer tumors. Moreover, B. longum-C-CPE-PE23 significantly suppressed tumor growth in mice with breast cancer without serious side effects, such as weight loss or hepatic and renal damage. We suggest that B. longum-C-CPE-PE23 is a good candidate for breast cancer treatment. Bifidobacterium could also be used as a drug delivery system for hepatotoxic agents.
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Enterococcus strains can compete, survive, and attach to host cells in the intestine, are highly resistant to a wide range of pH and temperature values, and can be used as a natural antimicrobial agent in the food industry.
“Other bacteria species such as Enterococcus are frequently used in the food industry today and present a key feature, which is the ability of the strains to compete, survive, and attach to host cells in the intestine [31]. Also, they are highly resistant to a wide range of pH and temperature values (these characteristics are attributed to their strong bacteriocin production capacity) and can be”
From The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties (2024) · cites this paper as [31]
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The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties
Maftei, N.-M., Raileanu, C. R., Balta, A. A., Ambrose, L., Boev, M., Marin, D. B., & Lisa, E. L. (2024) · Microorganisms · doi:10.3390/microorganisms12020234 · Cited by 381 · see citing works
- Authors
- Shimizu, Y., Isoda, K., Taira, Y., Taira, I., Kondoh, M., & Ishida, I.
- Affiliations
- Teikyo Heisei University (JP)
- The University of Osaka (JP)
- Corresponding author
- Shimizu, Yoshimi
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 887
- Pages
- 173596
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W3087816217
- Cited by
- 32
- References
- 34
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 12 · 2023: 1 · 2022: 6 · 2021: 1
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Private School Promotion Foundation
- Japan Society for the Promotion of Science (18K06755, 19H04468, 19K16452, 20H03392)
- Ministry of Education, Culture, Sports, Science and Technology
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- Bifidobacterium longum, claudin-4, Clostridium perfringens enterotoxin, recombinant bacteria, anticancer drug delivery, triple-negative breast cancer, tumor growth inhibition, hepatotoxicity, bacterial secretome
- MeSH terms
- Animals, Antineoplastic Agents, Bifidobacterium, DNA, Recombinant, Dose-Response Relationship, Drug, Enterotoxins, Female, Humans, Mice, Inbred BALB C, Plasmids, Drug Delivery Systems, Cell Line, Tumor, Mice, Claudins, Claudin-4, Triple Negative Breast Neoplasms
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