Interplay of gut microbiome, fatty acids, and the endocannabinoid system in regulating development, progression, immunomodulation, and chemoresistance of cancer

Nandi, Sourav Kumar; Basu, Sandip K.; Bhattacharjya, Anish; Ghosh, Ruma Dey; Bose, Chinmoy K; Mukhopadhyay, Soma; Bhattacharya, R.K.

doi:10.1016/j.nut.2022.111787

Cited by 4 publications

(3 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As described above, these fatty acids can also be generated from alpha-linoleic acid through a series of elongation and desaturation steps, although the efficiency of conversion is limited. Upon consumption, these fatty acids will target the composition and function of the gut microbiota [6–10], which has functional consequences. There is compelling evidence that long-chain n-3 PUFAs specifically control the composition and function of the gut microbiome of rodents and humans [11,12].…”

Section: Sources Of Heterogeneity In the Response To N-3 Polyunsatura...mentioning

confidence: 99%

Heterogeneity in the response to n-3 polyunsaturated fatty acids

Shaikh

Bazinet

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

Purpose of reviewA central goal in the study of long chain n-3 polyunsaturated fatty acids (PUFA) is to translate findings from the basic sciences to the population level to improve human health and prevent chronic diseases. A tenet of this vision is to think in terms of precision medicine and nutrition, that is, stratification of individuals into differing groups that will have different needs across the lifespan for n-3 PUFAs. Therefore, there is a critical need to identify the sources of heterogeneity in the human population in the dietary response to n-3 PUFA intervention.Recent findingsWe briefly review key sources of heterogeneity in the response to intake of long chain n-3 PUFAs. These include background diet, host genome, composition of the gut microbiome, and sex. We also discuss the need to integrate data from newer rodent models (e.g. population-based approaches), multi -omics, and analyses of big data using machine learning and data-driven cluster analyses.SummaryAccounting for vast heterogeneity in the human population, particularly with the use of big data integrated with preclinical evidence, will drive the next generation of precision nutrition studies and randomized clinical trials with long-chain n-3 PUFAs.

show abstract

Section: Sources Of Heterogeneity In the Response To N-3 Polyunsatura...mentioning

confidence: 99%

Heterogeneity in the response to n-3 polyunsaturated fatty acids

Shaikh

Bazinet

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

View full text Add to dashboard Cite

show abstract

“…In this process, Glutathione Peroxidase 4 (GPX4) is the most important regulator of iron death-related mechanisms, and RSL3, as a small-molecule inhibitor of GPX4, is currently the most commonly used Ferroptosis inducer [20][21][22][23][24][25]. Moreover, the endocannabinoid system exerts anticarcinogenic effects via multiple mechanisms, including proapoptotic and antiproliferative properties [26][27][28]. Fatty acid amide hydrolase (FAAH), a member of the serine hydrolase family of enzymes, was first identified as the principal catabolic enzyme that catalyzes the hydrolysis of endogenous amidated lipids such as N arachidonoylethanolamine (AEA, anandamide), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), which regulating various metabolic pathways and pathophysiological conditions in the body, such as emotion, cognition, energy balance, pain sensation, neuroinflammation, and cancer cell proliferation [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway

et al. 2023

View full text Add to dashboard Cite

Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with ferroptosis inducer (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and cytosolic reactive oxygen species (ROS). In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the phosphatidylinositol 3 kinase (PI3K)-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.

show abstract

“…The endocannabinoid system exerts anticarcinogenic effects via multiple mechanisms, including proapoptotic and antiproliferative properties [26][27][28]. Fatty acid amide hydrolase (FAAH), a member of the serine hydrolase family of enzymes, was rst identi ed as the principal catabolic enzyme that hydrolyzes several endogenous ligands, mainly anandamide (AEA) and 2-arachidonic glycerol, which regulate various pathophysiological conditions in the body, such as emotion, cognition, energy balance, pain sensation, neuroin ammation, and cancer cell proliferation [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway

Hao

Chen

Feng

et al. 2022

Preprint

View full text Add to dashboard Cite

Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde, 4-hydroxynonenal, and cytosolic reactive oxygen species. In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the PI3K-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.

show abstract

Interplay of gut microbiome, fatty acids, and the endocannabinoid system in regulating development, progression, immunomodulation, and chemoresistance of cancer

Cited by 4 publications

References 87 publications

Heterogeneity in the response to n-3 polyunsaturated fatty acids

Heterogeneity in the response to n-3 polyunsaturated fatty acids

Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway

Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway

Contact Info

Product

Resources

About