Effect of extracellular vesicles of Lactobacillus rhamnosus GG on the expression of CEA gene and protein released by colorectal cancer cells

Abstract

Background and Objectives: Almost all living cells secret nano-sized structures enclosed by the lipid bilayer called extra- cellular vesicles (EVs) into their extracellular milieu. These EVs play important roles in several physiological processes as a cargo delivery system. In probiotics, EVs are the main communication tool with the host. The present study aimed to assess the effect of EVs originated from Lactobacillus rhamnosus GG on the Carcinoembryonic antigen (cea) gene expression and protein (CEA) synthesis in the SW480 and HT-29 cell lines.
 Materials and Methods: Different concentrations of Lactobacillus rhamnosus GG EVs were applied on the SW480 and HT-29 cell lines. The MTT assay, Real-Time PCR, and ELISA analysis methods were exploited to explore the cell viability and the expression level of the cea gene in comparison with the β-actin gene as the control.
 Results: The two concentrations of 80 and 100 μg/ml of Lactobacillus rhamnosus GG EVs considerably affected the an- ti-proliferation and increased the amount of both CEA mRNA and protein (p < 0.05).
 Conclusion: Our findings showed that EVs of Lactobacillus rhamnosus GG could induce the gene expression and protein synthesis of CEA. Also, they reduced the cell proliferation of HT29 and SW480. Thus, probiotics such as EVs of Lactoba- cillus rhamnosus GG could be useful for preventing colorectal cancer.

Dietary Lactobacillus rhamnosus GG extracellular vesicles enhance antiprogrammed cell death 1 (anti-PD-1) immunotherapy efficacy against colorectal cancer

“…3c) and MC38 (Fig. 3d) colorectal cancer cells was reduced in a concentration-dependent manner after treatment with different concentrations of LGG-EV for 24 h. These results suggested that, as in a previous study, 32 LGG-EV have an antiproliferative effect on cancer cells in vitro .…”

Extracellular Vesicles of Probiotics: Shedding Light on the Biological Activity and Future Applications

“…Given these results, we can assume that, unsurprisingly, not all probiotic strains may have the same health-promoting potential, although engineered EVs could represent a promising tool in cancer therapies. The remaining two articles [ 56 , 57 ] noted the same EVs’ properties on HepG2, SW480, and HT29 cells, highlighting an anti-proliferative effect on cancer cell lines ( Table 2 ). According to Behzadi et al [ 56 ], L. rhamnosus -EVs can increase the apoptotic index ( bax / bcl2 expression ratio) in liver cancer cells in a dose-dependent manner.…”

“…Among the 60 of them, 15 and 45 concerned Gram-negative and Gram-positive bacteria, respectively. All articles assessed the size of the produced EVs, of which 49 determined it using only one technique (21 with electron microscopy [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ], 19 with NTA [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ], and 9 with DLS [ 42 , 45 , 49 , 50 , 91 , 92 ,…”

“…According to Behzadi et al [ 56 ], L. rhamnosus -EVs can increase the apoptotic index ( bax / bcl2 expression ratio) in liver cancer cells in a dose-dependent manner. Keyhani et al [ 57 ], analyzing EVs of the same probiotic strain, reported an inhibitory effect on colon cancer cells too. Otherwise, in the latter article, a specific mechanism of action was not considered.…”

Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant

“…Interestingly, it was recently discovered that sterile cellfree supernatant from LGG culture may promote the activity of formyl peptide receptor 1 (FPR1), which is an innate immune sensor of bacteria with anti-inflammatory and anti-angiogenic potential, expressed by both HCT-116 and HT-29 [40]. Moreover, it was proven that LGG-secreted anti-cancer biomolecule(s) may be transported within LGG-derived extracellular vesicles, with the capability to actively reduce the proliferation rate of both HT-29 and SW480 [41]. Also, nanoparticles loaded with LGG cytoplasmic lysate could significantly reduce HT-29 viability and promote apoptosis [42].…”