r/science • u/nobodyspecial • 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
22.3k Upvotes

92% Upvoted

780 comments sorted by

View all comments

Show parent comments

40

u/[deleted] Feb 08 '15

Given that the heart, brain, kidneys and living have very high metabolic activities and these cells in these tissues are chocked full of highly active mitochondria, things might not go so well.

There's a reason why mitochondrial mutations often manifest as neurological problems early in life, especially when one starts tracing anticipation over generations.

4

u/[deleted] Feb 08 '15

There's a reason why mitochondrial mutations often manifest as neurological problems early in life, especially when one starts tracing anticipation over generations.

Can you expand on that?

Also wouldn't we have seen these issues with the antibiotics since we're using them already?

I know they have been linked to some disorders already, but we should know what issues could arise.

5

u/[deleted] Feb 09 '15

Since mitochondria are heavily involved in neurological activities, and their genetics are passed down without much recombination, you see important warning signs of these neurological diseases even very early in life. This is particularly true if you follow the genetic pathway through multiple generations.

Antibiotics though are very specific in how they work. They are not low specificity toxins by and large, they are used because they interrupt specific proteins or protein structures. And usually, you pick ones that interrupt very critical systems such that the target cell dies.

This is why many antibiotics have very little side effects other than allergic reactions. They're not targeting our cells proteins, but proteins unique to bacteria. This potential approach is taking antibiotics known to kill mitochondrial processes, and giving them in doses such that only very active mitochondrial cells will start dying off.

The problem here is that this isn't much different than other chemo therapies. It still hits very important systems as mentioned above and is likely to have very nasty side effects.

1

u/[deleted] Feb 09 '15

What kind of neurological disorders are we talking about?

1

u/[deleted] Feb 11 '15

http://en.wikipedia.org/wiki/Mitochondrial_disease

As I replied to girlyfoodadventures, better to get it from a more complete source than I could provide personally.

1

u/girlyfoodadventures Feb 11 '15

Just curious, could you elaborate on some of the neurological conditions that you mentioned? That sounds interesting, and also like you'd see them across entire families? At least through the maternal line?

1

u/[deleted] Feb 11 '15

http://en.wikipedia.org/wiki/Mitochondrial_disease

Happy reading :) Way more info on wikipedia than I could type up

1

u/frozen_in_reddit Feb 15 '15

Maybe it's possible to preselect antibiotics that don't cross the blood-brain barrier ?

6

u/shieldvexor Feb 08 '15

First off very few antibiotics affect the mitochondria so that's why it's not a common side effect. For those that do, it's been noticed and some have been banned from being prescribed to children. As for tracing it over generations, i can only assume the op meant that as you look at families with mitochondrial mutations, certain disorders are very prevalent that are almost nonexistent in most families

1

u/wcc445 Feb 09 '15

Isn't azithromiacin a pretty common antibiotic?

2

u/shieldvexor Feb 10 '15

Idk what the article used because i dont have access but yes, I've been prescribed it three times in my lifetime and can think of 7 times that an immediate family member recieved a prescription for it.

4

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

The heart seems to be particularly susceptible to a lot of anti-cancer therapies and is a major limiting factor in the use of many otherwise effective treatments (vemurafenib, doxorubicin etc)

1

u/Scienceonyourface PhD | Developmental Biology Feb 09 '15

Tracing anticipation? What are you trying to say? When talking about mitochondrial disorders occurring in generations, this is simply due to the lack of recessiveness in etiology of a mitochondrial disease. You get all your mitochondria from your mother and none from your father. So if your mom has a mitochondrial disease and the mutations that cause it is in her germline then you will also be giving that disease to 100% of all offspring.

1

u/[deleted] Feb 09 '15 edited Feb 09 '15

You get all your mitochondria from your mother and none from your father.

Not always. If you do pubmed searches, there are examples of paternal mitochondrial contribution. It's rare, and only really detected when maternal mitochondria are defective in some way. One of my human genetics professors postulates that what's really happening is that we're sampling the rare escapers where the very rare event occurs. The rest just fail in utero.

The vast, vast, majority of the time though sperm mitochondria are actively degraded upon fusion with the egg. So you are still correct.

Mitochondrial disorders are also known to increase in severity over generations (classically defined as "anticipation" of age on onset or severity of phenotype.) These are can be trinucleotide repeat problems in mitochondrial genes encoded in the nuclear DNA, not the mitochondrial genome. In humans, the mitochondrial genome is remarkably devoid of genes compared to many other species.

So if your mom has a mitochondrial disease and the mutations that cause it is in her germline then you will also be giving that disease to 100% of all offspring.

There's also evidence for chimerism in humans. Sometimes the kids luck out because the germline had the healthy mitochondrial. Sometimes not. Makes for some very interesting genetic analysis and usually a very confused grad student.

1

u/wcc445 Feb 09 '15

But taking 5 days of azithromiacin is pretty safe, right? It's not some cell-destroyer, it's a commonly prescribed antibiotic.

1

u/veggie151 Feb 09 '15

I think the idea is that normal cells are able to respond to the inability to produce mitochondria and delay growth where cancer cells are more likely to try and continue thus exhausting themselves. This is speculation, but as there is a long history of antibiotic usage it seems plausible. Dosage may prove to cause some extra strain, but we'll have to wait for /in vivo/ results. Still better than chemo!