Toxic effects of microbial phenolic acids on the functions of mitochondria

Федотчева, Н. И.; Казаков, Р. Е.; Кондрашова, М. Н.; Белобородова, Н. В.

doi:10.1016/j.toxlet.2008.06.861

Cited by 49 publications

(41 citation statements)

References 44 publications

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“…Interestingly, it is also known that low-molecular-weight phenolic acids can produce both cytoprotective and cytotoxic effects in different settings, 33 including cytotoxicity toward breast cancer in in vitro and in vivo experiments. 34 However, details are still scarce regarding their mechanisms of action.…”

Section: ' Discussionmentioning

confidence: 99%

Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against Human Breast Cancer Cells

Serafim

Carvalho

Marques

et al. 2011

Chem. Res. Toxicol.

121

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In the present work, lipophilic caffeic and ferulic acid derivatives were synthesized, and their cytotoxicity on cultured breast cancer cells was compared. A total of six compounds were initially evaluated: caffeic acid (CA), hexyl caffeate (HC), caffeoylhexylamide (HCA), ferulic acid (FA), hexyl ferulate (HF), and feruloylhexylamide (HFA). Cell proliferation, cell cycle progression, and apoptotic signaling were investigated in three human breast cancer cell lines, including estrogen-sensitive (MCF-7) and insensitive (MDA-MB-231 and HS578T). Furthermore, direct mitochondrial effects of parent and modified compounds were investigated by using isolated liver mitochondria. The results indicated that although the parent compounds presented no cytotoxicity, the new compounds inhibited cell proliferation and induced cell cycle alterations and cell death, with a predominant effect on MCF-7 cells. Interestingly, cell cyle data indicates that effects on nontumor BJ fibroblasts were predominantly cytostatic and not cytotoxic. The parent compounds and derivatives also promoted direct alterations on hepatic mitochondrial bioenergetics, although the most unexpected and never before reported one was that FA induces the mitochondrial permeability transition. The results show that the new caffeic and ferulic acid lipophilic derivatives show increased cytotoxicity toward human breast cancer cell lines, although the magnitude and type of effects appear to be dependent on the cell type. Mitochondrial data had no direct correspondence with effects on intact cells suggesting that this organelle may not be a critical component of the cellular effects observed. The data provide a rational approach to the design of effective cytotoxic lipophilic hydroxycinnamic derivatives that in the future could be profitably applied for chemopreventive and/or chemotherapeutic purposes.

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Section: ' Discussionmentioning

confidence: 99%

Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against Human Breast Cancer Cells

Serafim

Carvalho

Marques

et al. 2011

Chem. Res. Toxicol.

121

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“…The level of hydroxyphenyllactic acid is elevated in patients with inherited deficiency of the enzyme p -hydroxyphenylpyruvate oxidase (Wishart et al, 2009) and we observed no difference in the level of this compound among our cohorts. Phenolic compounds may influence a range of cellular functions including differentiation, apoptosis, mitochondrial function, and inflammation (Li et al, 2004; Karlsson et al, 2005; Fedotcheva et al, 2008). …”

Section: Discussionmentioning

confidence: 99%

Profiles of Microbial Fatty Acids in the Human Metabolome are Disease-Specific

Ktsoyan¹,

Белобородова²,

Sedrakyan³

et al. 2011

Front. Microbio.

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The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host–microbe co-evolution and co-adaptation. This tight integration creates intense cross-talk and signaling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication. Consequently, the composition of the human metabolome, which includes the gut metabolome, may be different in health and disease states in terms of microbial products and metabolites entering systemic circulation. To test this hypothesis, we measured the level of hydroxy, branched, cyclopropyl and unsaturated fatty acids, aldehydes, and phenyl derivatives in blood of patients with a hereditary autoinflammatory disorder, familial Mediterranean fever (FMF), and in patients with peptic ulceration (PU) resulting from Helicobacter pylori infection. Discriminant function analysis of a data matrix consisting of 94 cases as statistical units (37 FMF patients, 14 PU patients, and 43 healthy controls) and the concentration of 35 microbial products in the blood as statistical variables revealed a high accuracy of the proposed model (all cases were correctly classified). This suggests that the profile of microbial products and metabolites in the human metabolome is specific for a given disease and may potentially serve as a biomarker for disease.

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“…It turned out that some aromatic microbial metabolites are able to inhibit the NAD-dependent mitochondrial respiration. It is shown that the degree of inhibition depends on the chemical structure of metabolites [34]. In the experiment, in vitro the degree of inhibition of respiration of mitochondria by cinnamic acid was taken as 100% ( Figure 5).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Interaction of Host‐Microbial Metabolism in Sepsis

Владимировна¹

2017

Sepsis

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The majority of species of the human gut microbiota is not cultivated on artiicial nutrient media, but they are included in the functioning of microbial metabolic conveyor. Between the numerous gut bacteria (transmiter) and billions of intracellular mitochondria (receiver), the function of signaling molecules performs aromatic metabolites. Sepsis destroys the coordinated work of the indigenous anaerobic microlora. This leads to the imbalance of aromatic microbial metabolites (AMM). We hypothesized and proved diagnostic and pathogenic signiicance of this. First, deiciency of the end products of microbial metabolism-lipophilic AMM (PhPA and derivatives-cinnamic and benzoic acids) in sepsis, and second, excessive accumulation in blood of intermediate products named, "sepsis-associated" AMM-both lead to the development of mitochondrial dysfunction. Particularly, the total suppressed production of mROS can manifest by "hibernate-like state" of cells and lead to MOF. The participation of aromatic metabolites in the development of septic shock can be explained by the inhibition of tyrosine hydroxylase and impaired synthesis of catecholamines. In clinical research, the high levels of "sepsis-associated" AMM (p-HPhAA, p-HPhLA, and PhLA) correlate with the severity according to APACHE II, Sepsis-related Organ Failure Assessments (SOFA) score and mortality. To improve the survival of ICU patients, requires more atention to the role of imbalance of microbial metabolites in sepsis.

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Toxic effects of microbial phenolic acids on the functions of mitochondria

Cited by 49 publications

References 44 publications

Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against Human Breast Cancer Cells

Lipophilic Caffeic and Ferulic Acid Derivatives Presenting Cytotoxicity against Human Breast Cancer Cells

Profiles of Microbial Fatty Acids in the Human Metabolome are Disease-Specific

Interaction of Host‐Microbial Metabolism in Sepsis

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