Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant
Abstract Background Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04036-3 |
| _version_ | 1827982899267239936 |
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| author | Rossella Salemi Silvia Vivarelli Daria Ricci Marina Scillato Maria Santagati Giuseppe Gattuso Luca Falzone Massimo Libra |
| author_facet | Rossella Salemi Silvia Vivarelli Daria Ricci Marina Scillato Maria Santagati Giuseppe Gattuso Luca Falzone Massimo Libra |
| author_sort | Rossella Salemi |
| collection | DOAJ |
| description | Abstract Background Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized in clinics to alleviate diarrhea, mucositis or intestinal damage which might be associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy or radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) might exert anti-proliferative activity toward colon cancer and metastatic melanoma cells. Moreover, we assess the potential adjuvant effect of LGG-SN in combination with anti-cancer drugs. Methods LGG-SN alone or in combination with either 5-Fuorouracil and Irinotecan was used to treat human colon and human melanoma cancer cell lines. Dimethylimidazol-diphenyl tetrazolium bromide assay was employed to detect cellular viability. Trypan blue staining, anti-cleaved caspase-3 and anti-total versus anti-cleaved PARP western blots, and annexin V/propidium iodide flow cytometry analyses were used to assess cell death. Flow cytometry measurement of cellular DNA content (with propidium iodide staining) together with qPCR analysis of cyclins expression were used to assess cell cycle. Results We demonstrate that LGG-SN is able to selectively reduce the viability of cancer cells in a concentration-dependent way. While LGG-SN does not exert any anti-proliferative activity on control fibroblasts. In cancer cells, the reduction in viability is not associated with apoptosis induction, but with a mitotic arrest in the G2/M phase of cell cycle. Additionally, LGG-SN sensitizes cancer cells to both 5-Fluorouracil and Irinotecan, thereby showing a positive synergistic action. Conclusion Overall, our results suggest that LGG-SN may contain one or more bioactive molecules with anti-cancer activity which sensitize cancer cells to chemotherapeutic drugs. Thus, LGG could be proposed as an ideal candidate for ground-breaking integrated approaches to be employed in oncology, to reduce chemotherapy-related side effects and overcome resistance or relapse issues, thus ameliorating the therapeutic response in cancer patients. |
| first_indexed | 2024-04-09T22:40:22Z |
| format | Article |
| id | doaj.art-495673a6b4d14813a8ab689af18fa307 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T22:40:22Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-495673a6b4d14813a8ab689af18fa3072023-03-22T12:14:24ZengBMCJournal of Translational Medicine1479-58762023-03-0121111710.1186/s12967-023-04036-3Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvantRossella Salemi0Silvia Vivarelli1Daria Ricci2Marina Scillato3Maria Santagati4Giuseppe Gattuso5Luca Falzone6Massimo Libra7Department of Biomedical and Biotechnological Sciences, Section of General Pathology, Clinics and Oncology, University of CataniaDepartment of Biomedical and Biotechnological Sciences, Section of General Pathology, Clinics and Oncology, University of CataniaDepartment of Biomedical and Biotechnological Sciences, Section of General Pathology, Clinics and Oncology, University of CataniaDepartment of Biomedical and Biotechnological Sciences, Section of Microbiology, University of CataniaDepartment of Biomedical and Biotechnological Sciences, Section of Microbiology, University of CataniaDepartment of Biomedical and Biotechnological Sciences, Section of General Pathology, Clinics and Oncology, University of CataniaEpidemiology and Biostatistics Unit, Istituto Nazionale Tumori IRCCS Fondazione G. PascaleDepartment of Biomedical and Biotechnological Sciences, Section of General Pathology, Clinics and Oncology, University of CataniaAbstract Background Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well as to improve the efficacy of certain anti-cancer treatments. Among the most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized in clinics to alleviate diarrhea, mucositis or intestinal damage which might be associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy or radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) might exert anti-proliferative activity toward colon cancer and metastatic melanoma cells. Moreover, we assess the potential adjuvant effect of LGG-SN in combination with anti-cancer drugs. Methods LGG-SN alone or in combination with either 5-Fuorouracil and Irinotecan was used to treat human colon and human melanoma cancer cell lines. Dimethylimidazol-diphenyl tetrazolium bromide assay was employed to detect cellular viability. Trypan blue staining, anti-cleaved caspase-3 and anti-total versus anti-cleaved PARP western blots, and annexin V/propidium iodide flow cytometry analyses were used to assess cell death. Flow cytometry measurement of cellular DNA content (with propidium iodide staining) together with qPCR analysis of cyclins expression were used to assess cell cycle. Results We demonstrate that LGG-SN is able to selectively reduce the viability of cancer cells in a concentration-dependent way. While LGG-SN does not exert any anti-proliferative activity on control fibroblasts. In cancer cells, the reduction in viability is not associated with apoptosis induction, but with a mitotic arrest in the G2/M phase of cell cycle. Additionally, LGG-SN sensitizes cancer cells to both 5-Fluorouracil and Irinotecan, thereby showing a positive synergistic action. Conclusion Overall, our results suggest that LGG-SN may contain one or more bioactive molecules with anti-cancer activity which sensitize cancer cells to chemotherapeutic drugs. Thus, LGG could be proposed as an ideal candidate for ground-breaking integrated approaches to be employed in oncology, to reduce chemotherapy-related side effects and overcome resistance or relapse issues, thus ameliorating the therapeutic response in cancer patients.https://doi.org/10.1186/s12967-023-04036-3Lactobacillus rhamnosus GGLGGCancerAdjuvantCombination therapies |
| spellingShingle | Rossella Salemi Silvia Vivarelli Daria Ricci Marina Scillato Maria Santagati Giuseppe Gattuso Luca Falzone Massimo Libra Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant Journal of Translational Medicine Lactobacillus rhamnosus GG LGG Cancer Adjuvant Combination therapies |
| title | Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant |
| title_full | Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant |
| title_fullStr | Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant |
| title_full_unstemmed | Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant |
| title_short | Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant |
| title_sort | lactobacillus rhamnosus gg cell free supernatant as a novel anti cancer adjuvant |
| topic | Lactobacillus rhamnosus GG LGG Cancer Adjuvant Combination therapies |
| url | https://doi.org/10.1186/s12967-023-04036-3 |
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