Characterization of the Anti-Cancer Activity of the Probiotic Bacterium Lactobacillus fermentum Using 2D vs. 3D Culture in Colorectal Cancer Cells

Lee, Jooeun; Lee, Jina; Kim, Ji Hyun; Cho, Namki; Lee, Sung Hoon; Park, Sung Bum; Koh, Byumseok; Kang, Dukjin; Kim, Seil; Yoo, Hee Min

doi:10.3390/biom9100557

Cited by 50 publications

(28 citation statements)

References 41 publications

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“…Their culture supernatants inhibited the growth of cancerous cells by up to 7% after 72 h of incubation at the concentration of 25%. Our study confirms a previous finding by Lee et al (2019), who demonstrated the antiproliferative effects of the culture-free supernatant (CFS) of a L. fermentum strain against colorectal cancer (CRC). It was shown that the CFS induces apoptosis, thereby inhibiting cell growth in CRC lines.…”

Section: Discussionsupporting

confidence: 92%

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Isolation of Novel Probiotic Lactobacillus and Enterococcus Strains From Human Salivary and Fecal Sources

et al. 2020

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Probiotics are non-pathogenic microorganisms that can interact with the gastrointestinal microbiota. They have numerous beneficial health effects that include enhancement of the host immune response, antiallergic, antimicrobial, anti-cancer, and anti-inflammatory properties. Probiotics are capable of restoring the impaired microbiome of a dysbiotic gut. They can be isolated from different environments. However, it is frequently suggested that probiotics for human use should come from human sources. The objective of this study was to isolate and characterize novel probiotic strains from the saliva and feces of healthy human individuals. To meet the criteria for probiotic attributes, the isolates were subjected to numerous standard morphological and biochemical tests. These tests included Gram staining, catalase tests, antibiotic susceptibility testing, hemolytic and antagonistic evaluation, tolerance tests involving temperature, NaCl levels, pH and bile salts, adherence ability assays, and genotypic characterization involving 16S rRNA gene sequencing. From 26 saliva and 11 stool samples, 185 microbial strains were isolated. Based on morphological and biochemical characteristics, 14 potential probiotic candidates were selected and identified genotypically. The new strains belonged to Lactobacillus fermentum, Enterococcus faecium, and Enterococcus hire. The selected strains were non-hemolytic, showed high tolerance to low pH and bile salts, and strong adherence abilities. Furthermore, the strains displayed a wide range of antimicrobial activities, particularly against antibiotic-resistant pathogens such as methicillin resistant Staphylococcus aureus (MRSA). Moreover, five of the selected isolates demonstrated antiproliferative features against human colon cancer cell line (Caco-2). The results of this investigation confirm the diversity of microbial populations in the human gut and saliva, and since these strains are of human origin, they will highly likely display maximal activities in food and drugs set for human use. Hence, the new strains of this study require additional in vivo experiments to assess their health-promoting effects.

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Section: Discussionsupporting

confidence: 92%

“…The antiproliferative activity of L. fermentum is brought about by preventing NF-κB signaling. They showed that the Lactobacillus CFS is capable of inducing cell death, and thus has the potential to be used as a powerful multitarget anti-cancer chemotherapeutic agent (Lee et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Isolation of Novel Probiotic Lactobacillus and Enterococcus Strains From Human Salivary and Fecal Sources

et al. 2020

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“…P8 protein that produced by L. rhamnosus KCTC 12202BP, shows strong inhibitory effect on colon cancer cell by inducing cell cycle arrest [ 27 ]. And Lee et al evidenced the anti-cancer activity of the probiotic bacterium L. fermentum using 3D culture in colon cancer cells [ 28 ]. Moreover, Carmen et al revealed LAB shows anti-cancer effect by expressing antioxidant enzymes or IL-10 in colon cancer model mice [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway

Yue

Yang

et al. 2020

Microb Cell Fact

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Background Colorectal cancer (CRC) is a major clinical challenge, and the gut microbiome plays important roles in the occurrence and metastasis of CRC. Lactobacillus and their metabolites are thought to be able to suppress the growth of CRC cells. However, the antimetastatic mechanism of Lactobacillus or their metabolites toward CRC cells is not clear. Therefore, the aim of this study was to assess the inhibitory mechanism of cell-free supernatants (CFSs) of L. rhamnosus GG, L. casei M3, and L. plantarum YYC-3 on metastasis of CRC cells. Results YYC-3 CFS showed the highest inhibitory effect on CRC cell growth, invasion and migration, and inhibited MMP2, MMP9, and VEGFA gene and protein expression, and protein secretion. Furthermore, it suppressed the activities of MMPs by gelatin zymography. Moreover, the effective compounds in these CFSs were analyzed by Q Exactive Focus liquid chromatography–mass spectrometry. Conclusions Our results showed that metabolite secretions of YYC-3 may inhibited cell metastasis by downregulating the VEGF/MMPs signaling pathway. These data suggest that treatment of CRC cells with metabolites from L. plantarum YYC-3 may reduce colon cancer metastasis.

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“…Three-dimensional spheroid culture models represent in vivo cancer environments and can be used to study cell survival and drug resistance at the molecular mechanism level [ 12 ]. Three-dimensional Jurkat spheroid models were generated as described in our previous reports [ 22 , 23 ]. The cells were treated with 0.5% and 1.0% methylcellulose for 48 h and 72 h ( Figure 6 A).…”

Section: Resultsmentioning

confidence: 99%

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease

et al. 2021

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This study explores the potential anticancer effects of lesbicoumestan from Lespedeza bicolor against human leukemia cancer cells. Flow cytometry and fluorescence microscopy were used to investigate antiproliferative effects. The degradation of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) was evaluated using immunoprecipitation, Western blotting, and confocal microscopy. Apoptosis was investigated using three-dimensional (3D) Jurkat cell resistance models. Lesbicoumestan induced potent mitochondrial depolarization on the Jurkat cells via upregulated expression levels of mitochondrial reactive oxygen species. Furthermore, the underlying apoptotic mechanisms of lesbicoumestan through the MALT1/NF-κB pathway were comprehensively elucidated. The analysis showed that lesbicoumestan significantly induced MALT1 degradation, which led to the inhibition of the NF-κB pathway. In addition, molecular docking results illustrate how lesbicoumestan could effectively bind with MALT1 protease at the latter’s active pocket. Similar to traditional 2D cultures, apoptosis was markedly induced upon lesbicoumestan treatment in 3D Jurkat cell resistance models. Our data support the hypothesis that lesbicoumestan is a novel inhibitor of MALT1, as it exhibited potent antiapoptotic effects in Jurkat cells.

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Characterization of the Anti-Cancer Activity of the Probiotic Bacterium Lactobacillus fermentum Using 2D vs. 3D Culture in Colorectal Cancer Cells

Cited by 50 publications

References 41 publications

Isolation of Novel Probiotic Lactobacillus and Enterococcus Strains From Human Salivary and Fecal Sources

Isolation of Novel Probiotic Lactobacillus and Enterococcus Strains From Human Salivary and Fecal Sources

Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease

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