Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells

An, JaeJin; Ha, Eun-Mi

doi:10.1007/s12275-022-2201-1

Cited by 8 publications

(6 citation statements)

References 65 publications

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“…In this regard, however, we would like to point out that seven more original articles appeared during this time. These studies showed the protective effect of probiotic EVs on atopic dermatitis [ 139 ] and various intestinal pathologies (chemoresistant colorectal cancer [ 140 ] or intestinal infections made by enterotoxigenic E. coli [ 141 ]). It was also noticed that probiotic EVs have a strong immunomodulatory effect on the human body (including the intestines) [ 142 ], and that they can be used in the design of innovative vaccines against infectious diseases [ 143 ] and cancers [ 122 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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For many decades, the proper functioning of the human body has become a leading scientific topic. In the course of numerous experiments, a striking impact of probiotics on the human body has been documented, including maintaining the physiological balance of endogenous microorganisms, regulating the functioning of the immune system, enhancing the digestive properties of the host, and preventing or alleviating the course of many diseases. Recent research, especially from the last decade, shows that this health-benefiting activity of probiotics is largely conditioned by the production of extracellular vesicles. Although the importance of extracellular vesicles in the virulence of many live-threatening pathogens is widely described in the literature, much less is known with respect to the health-promoting effect of extracellular vesicles secreted by non-pathogenic microorganisms, including probiotics. Based on this, in the current review article, we decided to collect the latest literature data on the health-inducing properties of extracellular vesicles secreted by probiotics. The characteristics of probiotics’ extracellular vesicles will be extended by the description of their physicochemical properties and the proteome in connection with the biological activities exhibited by these structures.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…CRC cells that are 5-FU-resistant show cancer stem-cell-like properties and can induce early tumor recurrence or metastasis [ 51 , 52 ]. Therefore, novel therapeutic strategies are needed to overcome chemoresistance and increase the efficacy of anticancer drugs [ 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…L. plantarum and its metabolites have an inhibitory effect on chemoresistant CRC cells, especially 5-FU-resistant CRC cells [ 32 , 51 , 53 , 54 ]. L. plantarum can exhibit anticancer effects by increasing the cytotoxicity and death of CRC cells or reducing NLRP3 and ERK phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…Altered glycolysis increases glucose uptake and lactate production [ 42 ] and can promote acidic conditions, one of the hallmarks of cancer as well as chemoresistance [ 45 , 65 , 66 , 67 , 68 ]. However, L. plantarum metabolites can reverse altered glycolysis mechanisms, thereby decreasing cancer cell proliferation, increasing apoptosis, and decreasing chemoresistance [ 53 , 54 ]. Thus, L. plantarum metabolites can induce therapeutic effects and prevent cancer recurrence.…”

Section: Discussionmentioning

confidence: 99%

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Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses

et al. 2023

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Lactobacillus plantarum (L. plantarum) is a probiotic that has emerged as novel therapeutic agents for managing various diseases, such as cancer, atopic dermatitis, inflammatory bowel disease, and infections. In this study, we investigated the potential mechanisms underlying the anticancer effect of the metabolites of L. plantarum. We cultured L. plantarum cells to obtain their metabolites, created several dilutions, and used these solutions to treat human colonic Caco-2 cells. Our results showed a 10% dilution of L. plantarum metabolites decreased cell viability and reduced the expression of autophagy-related proteins. Moreover, we found co-treatment with L. plantarum metabolites and chloroquine, a known autophagy inhibitor, had a synergistic effect on cytotoxicity and downregulation of autophagy-related protein expression. In conclusion, we showed the metabolites from the probiotic, L. plantarum, work synergistically with chloroquine in killing Caco-2 cells and downregulating the expression of autophagy-related proteins, suggesting the involvement of autophagy, rather than apoptosis, in their cytotoxic effect. Hence, this study provides new insights into new therapeutic methods via inhibiting autophagy.

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“…Chemotherapeutic resistance is a major challenge in CRC treatment, and reprogramming of glucose metabolism is also associated with chemical drug resistance, and high glycolysis levels found in human CRC drug-resistant models ( Wang T. et al, 2018 ). Targeted inhibition of the glycolytic pathway can increase the sensitivity of CRC cells to chemotherapy drugs ( Cao et al, 2018 ; An and Ha, 2022 ). 5-FU is an important drug in first-line chemotherapy for CRC.…”

Section: Targeting Glycolysis In Colorectal Cancer Therapymentioning

confidence: 99%

Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action

Zhan,

Su,

et al. 2023

Front. Pharmacol.

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Colorectal cancer (CRC) is the third most common malignant tumor in the world, and it is prone to recurrence and metastasis during treatment. Aerobic glycolysis is one of the main characteristics of tumor cell metabolism in CRC. Tumor cells rely on glycolysis to rapidly consume glucose and to obtain more lactate and intermediate macromolecular products so as to maintain growth and proliferation. The regulation of the CRC glycolysis pathway is closely associated with several signal transduction pathways and transcription factors including phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), myc, and p53. Targeting the glycolytic pathway has become one of the key research aspects in CRC therapy. Many phytochemicals were shown to exert anti-CRC activity by targeting the glycolytic pathway. Here, we review the effects and mechanisms of phytochemicals on CRC glycolytic pathways, providing a new method of drug development.

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Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells

Cited by 8 publications

References 65 publications

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

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

Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses

Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action

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