The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells
IntroductionMany well-known risk factors for breast cancer are associated with dysbiosis (an aberrant microbiome). However, how bacterial products modulate cancer are poorly understood. In this study, we investigated the effect of an exopolysaccharide (EPS) produced by the commensal bacterium Bacill...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1292635/full |
| _version_ | 1797492577413365760 |
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| author | Mai R. Nguyen Mai R. Nguyen Emily Ma Emily Ma Debra Wyatt Katherine L. Knight Clodia Osipo Clodia Osipo |
| author_facet | Mai R. Nguyen Mai R. Nguyen Emily Ma Emily Ma Debra Wyatt Katherine L. Knight Clodia Osipo Clodia Osipo |
| author_sort | Mai R. Nguyen |
| collection | DOAJ |
| description | IntroductionMany well-known risk factors for breast cancer are associated with dysbiosis (an aberrant microbiome). However, how bacterial products modulate cancer are poorly understood. In this study, we investigated the effect of an exopolysaccharide (EPS) produced by the commensal bacterium Bacillus subtilis on breast cancer phenotypes. Although B. subtilis is commonly included in probiotic preparations and its EPS protects against inflammatory diseases, it was virtually unknown whether B. subtilis-derived EPS affects cancer.MethodsThis work investigated effects of EPS on phenotypes of breast cancer cells as a cancer model. The phenotypes included proliferation, mammosphere formation, cell migration, and tumor growth in two immune compromised mouse models. RNA sequencing was performed on RNA from four breast cancer cells treated with PBS or EPS. IKKβ or STAT1 signaling was assessed using pharmacologic or RNAi-mediated knock down approaches. ResultsShort-term treatment with EPS inhibited proliferation of certain breast cancer cells (T47D, MDA-MB-468, HCC1428, MDA-MB-453) while having little effect on others (MCF-7, MDA-MB-231, BT549, ZR-75-30). EPS induced G1/G0 cell cycle arrest of T47D cells while increasing apoptosis of MDA-MB-468 cells. EPS also enhanced aggressive phenotypes in T47D cells including cell migration and cancer stem cell survival. Long-term treatment with EPS (months) led to resistance in vitro and promoted tumor growth in immunocompromised mice. RNA-sequence analysis showed that EPS increased expression of pro-inflammatory pathways including STAT1 and NF-κB. IKKβ and/or STAT1 signaling was necessary for EPS to modulate phenotypes of EPS sensitive breast cancer cells. DiscussionThese results demonstrate a multifaceted role for an EPS molecule secreted by the probiotic bacterium B. subtilis on breast cancer cell phenotypes. These results warrant future studies in immune competent mice and different cancer models to fully understand potential benefits and/or side effects of long-term use of probiotics. |
| first_indexed | 2024-03-10T01:05:40Z |
| format | Article |
| id | doaj.art-a8ed490ebc1746b2845e2c786134e72d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-10T01:05:40Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a8ed490ebc1746b2845e2c786134e72d2023-11-23T14:27:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-11-011310.3389/fonc.2023.12926351292635The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cellsMai R. Nguyen0Mai R. Nguyen1Emily Ma2Emily Ma3Debra Wyatt4Katherine L. Knight5Clodia Osipo6Clodia Osipo7M.D./Ph.D. Program, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesDepartment of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesM.D./Ph.D. Program, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesIntegrated Cell Biology Program, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesDepartment of Cancer Biology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesDepartment of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesDepartment of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesDepartment of Cancer Biology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, United StatesIntroductionMany well-known risk factors for breast cancer are associated with dysbiosis (an aberrant microbiome). However, how bacterial products modulate cancer are poorly understood. In this study, we investigated the effect of an exopolysaccharide (EPS) produced by the commensal bacterium Bacillus subtilis on breast cancer phenotypes. Although B. subtilis is commonly included in probiotic preparations and its EPS protects against inflammatory diseases, it was virtually unknown whether B. subtilis-derived EPS affects cancer.MethodsThis work investigated effects of EPS on phenotypes of breast cancer cells as a cancer model. The phenotypes included proliferation, mammosphere formation, cell migration, and tumor growth in two immune compromised mouse models. RNA sequencing was performed on RNA from four breast cancer cells treated with PBS or EPS. IKKβ or STAT1 signaling was assessed using pharmacologic or RNAi-mediated knock down approaches. ResultsShort-term treatment with EPS inhibited proliferation of certain breast cancer cells (T47D, MDA-MB-468, HCC1428, MDA-MB-453) while having little effect on others (MCF-7, MDA-MB-231, BT549, ZR-75-30). EPS induced G1/G0 cell cycle arrest of T47D cells while increasing apoptosis of MDA-MB-468 cells. EPS also enhanced aggressive phenotypes in T47D cells including cell migration and cancer stem cell survival. Long-term treatment with EPS (months) led to resistance in vitro and promoted tumor growth in immunocompromised mice. RNA-sequence analysis showed that EPS increased expression of pro-inflammatory pathways including STAT1 and NF-κB. IKKβ and/or STAT1 signaling was necessary for EPS to modulate phenotypes of EPS sensitive breast cancer cells. DiscussionThese results demonstrate a multifaceted role for an EPS molecule secreted by the probiotic bacterium B. subtilis on breast cancer cell phenotypes. These results warrant future studies in immune competent mice and different cancer models to fully understand potential benefits and/or side effects of long-term use of probiotics.https://www.frontiersin.org/articles/10.3389/fonc.2023.1292635/fullprobioticsbreast cancerexopolysaccharidecommensal bacteriaIKK betaSTAT1 |
| spellingShingle | Mai R. Nguyen Mai R. Nguyen Emily Ma Emily Ma Debra Wyatt Katherine L. Knight Clodia Osipo Clodia Osipo The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells Frontiers in Oncology probiotics breast cancer exopolysaccharide commensal bacteria IKK beta STAT1 |
| title | The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells |
| title_full | The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells |
| title_fullStr | The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells |
| title_full_unstemmed | The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells |
| title_short | The effect of an exopolysaccharide probiotic molecule from Bacillus subtilis on breast cancer cells |
| title_sort | effect of an exopolysaccharide probiotic molecule from bacillus subtilis on breast cancer cells |
| topic | probiotics breast cancer exopolysaccharide commensal bacteria IKK beta STAT1 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1292635/full |
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