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Toxicity of antibiotics over Mitochondria can target cancer cells

pattismith

Senior Member
Messages
3,931
This thread is most of all to remind and warn about mito toxicity of Doxycycline and Azythromycin.

Many recent studies talk about their ability to target the cancer cells because of this property that inhibit cell multiplication (they inhibit bacteria multiplication as well).

An interesting thing I learnt in it is that N Acetyl Cystein partially reverses this inhibition (so we can wonder if NAC may inhibit the antibiotic effect as well!)

Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467100/


Induction of Mitochondrial Dysfunction and Oxidative Damage by Antibiotic Drug Doxycycline Enhances the Responsiveness of Glioblastoma to Chemotherapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584825/

Azithromycin effectively inhibits tumor angiogenesis by suppressing vascular endothelial growth factor receptor 2-mediated signaling pathways in lung cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494938/
 

Hip

Senior Member
Messages
17,824
Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467100/

I had a quick skim through this paper, and it does not talk about toxic effects on mitochondria, but rather the way these antibiotics inhibit mitochondrial biogenesis (the creation of new mitochondria).

In cells, mitochondria have a limited lifespan in the order of weeks (and some studies say just days), before they need to be decommissioned and replaced by new mitochondria, via the process of mitochondrial biogenesis.

The authors suggest that inhibiting mitochondrial biogenesis may prevent cancer stem cells from multiplying.



Some antibiotics do have mitochondrial toxicity though (see this post for a list of drugs with possible mitochondrial toxicity).
 

pattismith

Senior Member
Messages
3,931
I had a quick skim through this paper, and it does not talk about toxic effects on mitochondria, but rather the way these antibiotics inhibit mitochondrial biogenesis (the creation of new mitochondria).

In cells, mitochondria have a limited lifespan in the order of weeks (and some studies say just days), before they need to be decommissioned and replaced by new mitochondria, via the process of mitochondrial biogenesis.

The authors suggest that inhibiting mitochondrial biogenesis may prevent cancer stem cells from multiplying.

yes you are right, I thought too that it was more an inhibition process than pure toxicity (this is consistent with the bacteriostatic effect of these antibiotics)...But some other papers talk about real toxicity, like this one:


"doxycycline disrupted mitochondrial functions through decreasing mitochondrial membrane potential and mitochondrial respiration. Inducing mitochondrial dysfunctions by using doxycycline led to energy crisis, oxidative stress, and damage as shown by the decreased levels of ATP and the elevated levels of mitochondrial superoxide, intracellular ROS, 8-OHdG, protein carbonylation, and lipid peroxidation. An antioxidant N-acetyl-L-cysteine (NAC) significantly abolished the anti-proliferative and pro-apoptotic effects of doxycycline, demonstrating that doxycycline acts on glioblastoma via inducing oxidative stress."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584825/

We know that some bacteriostatic antibiotics can have bactericide effect at a higher dosage, so the effect on mitochondria (inhibition or toxicity) could be a matter of dosage?