Antibiotic Overusage Causes Mitochondrial Dysfunction Which May Promote Tumorigenesis

Elliott, Robert L.

doi:10.11648/j.jctr.20170504.11

Cited by 11 publications

(8 citation statements)

References 22 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have demonstrated in this presentation that antibiotics cause mitochondrial dysfunction, and have emphasized this in previous publications [19, 20]. Different groups of antibiotics cause mitochondrial damage by different mechanisms, but it is absolute that antibiotics cause mitochondrial damage.…”

Section: Discussionsupporting

confidence: 54%

The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: “Are cell culture data skewed?”

Elliott

Jiang

2019

PLoS ONE

View full text Add to dashboard Cite

Many cells are cultured in media that contains an antibiotic to prevent bacterial contamination. Mycoplasma and other bacterial contamination is a serious problem for those involved in cell culture. Antibiotics in the media helps prevent this contamination and make life easier for the investigators; as performing cell culture experiments in antibiotic free media is difficult and requires vigorous sterile technique. There are many reports of antibiotics causing mitochondrial damage. In this study, we tested the effect of gentamicin in culture media on human mammary epithelial MCF-12A and breast cancer MCF-7 and MDA-MB-231 cell lines by real time PCR, immunofluorescent microscopy, lactate assay, DNA damage assay. We found that the addition of gentamicin in media upregulated the gene expression of hypoxia inducer factor 1 alpha (HIF1a), glycolytic enzymes and glucose transporters, compared to the cells cultured in gentamicin free media. Gentamicin also increased the lactate production and inhibited mitochondrial membrane potential of the cell lines. Furthermore, the antibiotics in media induced mitochondrial reactive oxygen species causing DNA damage. We found an increase of 8-hydroxy-2’-deoxyguanosine a product of DNA oxidative damage in the media of MCF-12A, MCF-7 and MDA-MB-231 cell lines. These results showed that normal epithelial and breast cancer cells cultured in the media with gentamicin had increased HIF1a, aerobic glycolysis and DNA oxidative damage. If we use these unhealthy cells in the experiment, all data will be different, compared to cells grown in gentamicin free media. We have studied the detrimental effects of three antibiotics on mitochondrial function in the untransformed MCF-12A human mammary cell line and two human mammary cancer cell lines, MCF-7 and MB-MDA-231. The metabolic changes in all cell lines were dramatically different between those in antibiotic free media versus antibiotic containing media. There was a marked difference in gene expression of glycolytic enzymes, reactive oxygen species production and effects on membrane potential. Ironically, our first studies were done in media containing gentamicin, and repeated studies were done in gentamicin free media. The results were very different. The purpose of this report is to emphasize that metabolic cell culture data may be inaccurate because experiments were performed in cell culture media containing antibiotics. We will present evidence to support this theory.

show abstract

Section: Discussionsupporting

confidence: 54%

The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: “Are cell culture data skewed?”

Elliott

Jiang

2019

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Thus, almost all of the nonantibiotics mentioned above affect mitochondrial functions being either part of their modes of action or potential toxicities. Many antibiotics cause mitochondrial dysfunction, too, thus explaining their anti-neoplastic activities [30], or possibly promoting tumorigenesis [265][266][267][268], obesity [269], and psychiatric disorders [270,271]. Thus, antibiotics as well as non-antibiotics exert beneficial or detrimental antimitochondrial activities.…”

Section: Conclusion and Open Questionsmentioning

confidence: 99%

Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?

Dalhoff

2020

Infection

View full text Add to dashboard Cite

Purpose Advances in structural biology, genetics, bioinformatics, etc. resulted in the availability of an enormous pool of information enabling the analysis of the ancestry of pro- and eukaryotic genes and proteins. Methods This review summarizes findings of structural and/or functional homologies of pro- and eukaryotic enzymes catalysing analogous biological reactions because of their highly conserved active centres so that non-antibiotics interacted with bacterial targets. Results Protease inhibitors such as staurosporine or camostat inhibited bacterial serine/threonine or serine/tyrosine protein kinases, serine/threonine phosphatases, and serine/threonine kinases, to which penicillin-binding-proteins are linked, so that these drugs synergized with β-lactams, reverted aminoglycoside-resistance and attenuated bacterial virulence. Calcium antagonists such as nitrendipine or verapamil blocked not only prokaryotic ion channels but interacted with negatively charged bacterial cell membranes thus disrupting membrane energetics and inducing membrane stress response resulting in inhibition of P-glycoprotein such as bacterial pumps thus improving anti-mycobacterial activities of rifampicin, tetracycline, fluoroquinolones, bedaquilin and imipenem-activity against Acinetobacter spp. Ciclosporine and tacrolimus attenuated bacterial virulence. ACE-inhibitors like captopril interacted with metallo-β-lactamases thus reverting carbapenem-resistance; prokaryotic carbonic anhydrases were inhibited as well resulting in growth impairment. In general, non-antibiotics exerted weak antibacterial activities on their own but synergized with antibiotics, and/or reverted resistance and/or attenuated virulence. Conclusions Data summarized in this review support the theory that prokaryotic proteins represent targets for non-antibiotics because of a common evolutionary origin of bacterial- and mammalian targets resulting in highly conserved active centres of both, pro- and eukaryotic proteins with which the non-antibiotics interact and exert antibacterial actions.

show abstract

“…We recently published a paper entitled "Antibiotic Overusage Causes Mitochondrial Dysfunction which May Promote Tumorigenesis" [1]. Some have considered this paper very controversial; however, it has been well received in the cancer metabolism community.…”

mentioning

confidence: 99%

Antibiotics Friend and Foe: “From Wonder Drug to Causing Mitochondrial Dysfunction, Disrupting Human Microbiome and Promoting Tumorigenesis”

Elliott¹,

Xian²,

Baucom³

et al. 2018

IJCM

View full text Add to dashboard Cite

Mitochondria are evolutionary bacteria that are dynamic intracellular organelles involved in many vital cellular functions. However, modern medicine has fallen prey to misuse and over-usage of antibiotics. This misuse can damage the mitochondrion, alter host antibiotic interactions, and cause serious pathophysiologic conditions. We believe this leads to mitochondrial dysfunction, which may promote tumorigenesis and neurodegeneration. This opinion commentary's goal is to bring awareness of this important hot topic to the medical community before induced modern plagues are irreversible.

show abstract

Antibiotic Overusage Causes Mitochondrial Dysfunction Which May Promote Tumorigenesis

Cited by 11 publications

References 22 publications

The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: “Are cell culture data skewed?”

The adverse effect of gentamicin on cell metabolism in three cultured mammary cell lines: “Are cell culture data skewed?”

Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?

Antibiotics Friend and Foe: “From Wonder Drug to Causing Mitochondrial Dysfunction, Disrupting Human Microbiome and Promoting Tumorigenesis”

Contact Info

Product

Resources

About