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 (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.

The inhibition effects of Lentilactobacillus buchneri-derived membrane vesicles on AGS and HT-29 cancer cells by inducing cell apoptosis

“…The study by Salemi et al revealed that the cell-free supernatant of L. rhamnosus GG (LGG-SN) specifically and concentration-dependently reduces the survival of cancer cells. For cancer cell lines, the relative IC 50 values vary from 91.8% LGG-SN (v/v) for the less sensitive Caco-2 cells to 73.8% LGG-SN (v/v) for HT-29 and 74.8% LGG-SN (v/v) for A375, respectively 57 . According to the MTT analysis of Vachkova et al Lacticaseibacillus paracasei strains can inhibit the growth of HT-29 cells in a dose-dependent manner 58 .…”

Characterization of Wnt signaling pathway under treatment of Lactobacillus acidophilus postbiotic in colorectal cancer using an integrated in silico and in vitro analysis

“…In line with our results, several studies confirmed the potential role of postbiotics in preventing and treating cancer, particularly CRC. By this means, Salami et al demonstrated that Lactobacillus rhamnosus GG could selectively reduce the viability of cancer cells, such as HT-29 cells, in a dose-dependent way, with a mitotic arrest the cell cycle in the G2/M phase 28 . Some studies, such as Shyu et al, focus on the anti-proliferative and apoptosis effects of Lactobacillus species in various cell lines.…”

“…Then, the pH of the postbiotics was brought to a physiological range (pH 7.2–7.4) by employing 5 M sodium hydroxide, and the solution was filtered through a 0.22 μm polyethersulfone membrane syringe filter (Millipore, USA). This process was carried out prior to conducting the anti-proliferation and anti-migration assays 28 .…”

Lactiplantibacillus plantarum Induces Apoptosis in Melanoma and Breast Cancer Cells

“…The cytotoxic activity in melanoma cells was comparable to the one recorded for the anticancer conventional drug 5-FU when LP was used in concentrations of 10 10 and 10 9 CFU/mL; similar concentrations of L. rhamnosus selectively reduced viability in A375 melanoma cells in a concentration-dependent manner [ 27 ]. 5-FU is usually associated with mucositis, diarrhea, myelosuppression, cardio- and neurotoxicity that make systemic treatment difficult for cancer patients; the use of LP may therefore replace a highly toxic anticancer therapy with a more acceptable one in terms of quality of life for the treated patients.…”