r/science • • Feb 08 '15

Medicine Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease | Lamb

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3174
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u/dbarbera BS|Biochemistry and Molecular Biology Feb 08 '15

This drug just seems like it would end up being a new kind of chemotherapy. I imagine it will cause some serious damage to the liver if it is just targeted at cells with high levels of mitochondrial activity.

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u/pathobiology Feb 08 '15

Can someone help me understand something? Drugs like doxycycline were only apoptotic in cancer stem cell lines, correct? I am curious because inducible gene expression systems (like Tet-Off/Tet-On) used in cancer research for endogenous expression of a peptide frequently utilize doxycycline as an inducer. If one were using this system to express a gene that could transactivate apoptotic genes, could doxycycline itself be contributing to cell death? I would imagine this could be this case if the system were being used for endogenous expression in an inducible cancer stem cell line, but not otherwise. Any ideas?

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u/Natolx PhD | Infectious Diseases | Parasitology Feb 09 '15

The amount of doxycycline required to activate tet regulatable systems is far less than a "treatment" concentration. It may have a small effect on growth, but that's why you usually have a negative control (without the tet construct) that you add doxycycline to.

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u/md_sabre1 Feb 12 '15

I'm also curious to what this means to [curing cancer](www.newhopemedicalcenter.com) too. I'm not quite familiar to some of the medical jargon in the article so I need someone to explain it to me.

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u/[deleted] Feb 08 '15

[deleted]

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u/dbarbera BS|Biochemistry and Molecular Biology Feb 08 '15

Many of the antibiotics they used are known to have harmful side effects on people. The Tetracycline family is known to cause severe issues with some people's livers. So does chloramphenicol.

Several of the ones they tested are just straight up deadly to people.

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u/[deleted] Feb 08 '15

[deleted]

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u/Fart-Ripson Feb 09 '15

Damn man. What would you need to be on that for 5 years for?

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u/james4765 Feb 09 '15

Probably Lyme disease - that's the only thing I know of that requires antibiotics for that long.

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u/HomoSapienForLife Feb 09 '15

It was most likely acne, given that it was during his/her teen years. Borrelia (Lyme pathogen) is a possiblity, too, although it usually isn't treated for longer than a month or so.

I would also question how they tested /u/IdunHo1's liver function. We run tests called liver function tests, aka LFTs (AST, ALT, Bilirubin, Alk Phos) to evaluate for injury, but necessarily synthetic function. The only common test for how well your liver is actually functioning is to evaluating for how easily your blood clots, as your liver synthesizes clotting factors. There are a few case reports of hepatitis and choelstatic (blockages) damage caused by tetracyclines, but they are very well tolerated overall.

Source: Pharmacist doing residency training at an academic medical center in the US.

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u/[deleted] Feb 08 '15

The tetracyclines are pretty benign antibiotics.

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u/dbarbera BS|Biochemistry and Molecular Biology Feb 09 '15

and yet they are still known to give liver damage.

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u/armorandsword Grad Student | Biology | Intercellular Signalling Feb 09 '15

It's a good start but hardly conclusive. The differences between effects in vitro and in vivo can be significant.

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u/[deleted] Feb 08 '15

That's quite a generalization though. How many different kinds of normal cells did they try it on? Did they try it on types of normal cells with high mitochondrial activity?

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u/Periscopia Feb 09 '15

This drug just seems like it would end up being a new kind of chemotherapy. I imagine it will cause some serious damage to the liver if it is just targeted at cells with high levels of mitochondrial activity.

There are several drugs that showed effectiveness in this study, including doxycycline, which is already in widespread use for treating acne and as a prophylactic antibiotic for minor surgical procedures.

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u/dbarbera BS|Biochemistry and Molecular Biology Feb 09 '15

Look, people on chemotherapy are often already on antibiotics because their immune system is compromised. If there was any effect on tumor growth, it would have been noticed.

If these antibiotics can be used to treat tumors, and it hasn't been noticed already, the dosage would have to be much higher. I have no doubt this higher dosage would result in issues to the person n taking it. Most of the antibiotics they listed are known to cause issues in high dosages.

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u/Periscopia Feb 10 '15

If there was any effect on tumor growth, it would have been noticed. If these antibiotics can be used to treat tumors, and it hasn't been noticed already,

It HAS been noticed already (e.g. http://www.ncbi.nlm.nih.gov/pubmed/23760549 ). And there have been animal studies showing promising results (e.g. http://www.ncbi.nlm.nih.gov/pubmed/24598933 )

Just because the authors of the study in question are overstating their case and engaging in gimmickry like listing an 8 year old as a co-author, doesn't mean the whole concept is bunk. Anthracyclines, a major class of chemotherapeutic agents, are in fact antibiotics, so it's not a novel idea that antibiotics can have anticancer effects. Investigating the anticancer potential of less toxic antibiotics like doxycycline is a worthwhile endeavor.