Cancer cells wake up when people sleep | Hacker News Reader

Cancer cells wake up when people sleep

nature.com

145 pointsKasianFranks46 comments

In another summary at medicalXpress, the researchers mention melatonin

"Our research shows that the escape of circulating cancer cells from the original tumor is controlled by hormones such as melatonin, which determine our rhythms of day and night"

https://medicalxpress.com/news/2022-06-breast-cancer-night.h...

I was just going to mention melatonin related to this. I know that heavy doses of melatonin slow or kill cancer[citation needed].

And you have to think this is somehow related to this research.

Although you would expect the opposite of cancer growing at night, when melatonin is ostensibly at its highest (does it peak or start at 8PM?).

It would be good to know what the immune system is doing during sleep. As I understand it, metastasis is caused by a local depletion in nutrients or stress to the tumor cells, which then try to find a new environment to occupy. If tumor-killing activity of the immune system happens primarily at night, that could explain why metastasis is also primarily at night, and may explain the discrepancy on melatonin which you just mentioned, where this study found that higher melatonin levels correlated with higher circulating tumor cell numbers, but the literature suggests that melatonin helps kill tumors.

> where this study found that higher melatonin levels correlated with higher circulating tumor cell numbers, but the literature suggests that melatonin helps kill tumors.

Looks like a feedback cycle

>I know that heavy doses of melatonin slow or kill cancer

Melatonin is an antioxidant, which destroys chemicals known to cause cancer. I can't find info on it destroying cancer cells directly.

Well, FINALLY a scientific explanation about "sleep from 22:00 to 6:00, you'll be healthier" thing that is being constantly peddled!

It really pisses me off when people just keep repeating stuff and never support them with evidence.

This here however -- your tidbit -- is something I can work with and might prompt me to change my habits.

Any idea if taking melatonin pills while still going to bed at 4:00 is having the same, or at least some effect? Or does it not work at all then?

The problem is that sleep does so much, that even trying to create a list seems impossible, but some try: https://www.healthline.com/health/why-do-we-sleep

Sleep has been researched heavily (but far from conclusively), and there is an insane amount of diseases that people who don't get enough sleep are a risk group for. And some of those correlations are quite pronounced, like being ~30% more likely to get dementia if you don't get enough sleep in your 50s and 60s.

In some cases nobody can conclusively say whether there's causation, because we don't fully understand diseases like alzheimer or some of the processes happening during sleep, but in the meantime it seems prudent to sleep a healthy amount.

If you have the causation backwards in your phrasing, that implies that perhaps some people simply can't get good sleep even though they might try. You could say: you're 30% more likely to have sleep problems in your 50s and 60s if you're in the very early stages of developing dementia. Perhaps the disease process makes the sleep problems unavoidable and trying sleep more won't help.

Possibly. Without controlled trials we may never know certainly enough to satisfy some.

But considering the lifestyle loss from dementia I'd rather risk losing some waking time instead.

The hour you go to bed doesn’t matter. You need a regular sleep schedule with enough sleep and that’s it. What people mean, without realizing it, when they say the hours before midnight count double is that your first hours of sleep are the most important. Your sleep consists of several cycles, +- 90 minutes long. There are several stages of sleep in each cycle, deep sleep is the most important one. You are probably most familiar with the last stage, REM sleep. You get the most deep sleep in the first cycles, so in the first hours of sleeping. But it doesn’t matter when those first hours are, the body has no concept of midnight.

That's what I want to believe but many people say that melatonin peaks in your body during these hours so you should be asleep then to maximize the positive effect. Conversely, they say if you don't sleep during these hours then you're hugely increasing your health risks.

So I'm trying to figure out if they're right or not because I'm 42 and I've been a night owl since 12 and yeah, nowadays my health is quite bad and I'm busting my arse trying to fix it.

What does the sleep schedule of a self described night owl mean

There's none -- that's the best description, because it's not happening by schedule at all. Last night, for the first time in at least two months, I fell asleep at 3:00 AM. Usually it's 5:00 - 6:00.

Sometimes I sleep 4-5h and then have a huge nap -- 2.5h to 3.5h -- in the early evening. Happens for a week or two. Then I go without naps for a month.

It's relatively cyclical but the periods aren't with fixed values at all. The daily hours are fairly inconsistent as well.

Well that’s the issue then. You’re not getting enough sleep. And it’s not consistent.

Yep, but since I got a few health conditions I can no longer tell which one is the cause.

Guess I'll keep going to doctors like I do lately.

But I did hear from a few trainers and doctors that melatonin can be taken without prescription and is not dangerous, hence my question above.

I'll ask my doctor next time about it.

I have issues sleeping sporadically. I am a naturally hyper person - and found that if I do not make my body and/or my mind very tired, I cannot sleep deeply.

So I must complete heavy workouts every 1-2 days to make my body want to sleep. Maybe start heavy exercise when you feel you're getting near that point.

For me - it is a weight workout (lifting or power lifting). I can do a 1-2 hour cardio workout (or sprints) to get a similar effect.

Because most people are asleep during these hours, melatonin peaks when you sleep. Which for most people is 22:00 - 7:00 or something.

Your circadian rhythm regulates melatonin release. Not the clock hanging on your wall.

From your other comment, seems like your problem is a very inconsistent sleep pattern and not enough sleep.

There is plenty of actual science regarding sleep before midnight.

I would recommend googling rather than speculating in comment threads about unprescribed 'heavy doses' of unregulated supplements.

Sure, I'm doing that as well, in the meantime I'm curious if somebody has an experience.

>It really pisses me off when people just keep repeating stuff...

That's like %99.99 of "scientific" culture. People repeating stuff they heard. Memes.

Society isn't rational. Never was. Never will be.

There are pockets of relative rationality in society, and pockets of altruism, and sometimes they even overlap in time and proximity. It's a big mess, this society thing, but you know, just focus on being your best self and a good influence on what's around you. Don't let the broad view of humanity bring you down. It's probably a bit skewed by some jerks using your biases against you to get your attention and show you ads or something, and there's truth to the "life is what you make of it" platitudes.

(Is this post now a self-referential platitude? ...is it self-aware? Maybe I can convince that one Googler it's come to life.)

A lot of the literature suggests that it boosts the effects of chemotherapy. However chemotherapy damages host cells as well. It's unclear if melatonin promotes sparing of healthy cells that are dividing or simply boosts the effect of chemo everywhere.

REVIEWS:

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412427/

The melatonin immunomodulatory actions in radiotherapy https://pubmed.ncbi.nlm.nih.gov/28510090/

Usefulness of melatonin as complementary to chemotherapeutic agents at different stages of the angiogenic process https://www.nature.com/articles/s41598-020-61622-x

Role of melatonin in cancer treatment https://pubmed.ncbi.nlm.nih.gov/22753734/

Melatonin, a natural programmed cell death inducer in cancer https://pubmed.ncbi.nlm.nih.gov/22612707/

Cancer metastasis: Mechanisms of inhibition by melatonin https://pubmed.ncbi.nlm.nih.gov/27706852/

Melatonin and its ubiquitous anticancer effects https://pubmed.ncbi.nlm.nih.gov/31451998/

PRIMARY LIT:

Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis https://pubmed.ncbi.nlm.nih.gov/31970423/

RNA-Seq transcriptome analysis shows anti-tumor actions of melatonin in a breast cancer xenograft model https://pubmed.ncbi.nlm.nih.gov/30700756/

Effect of melatonin on T/B cell activation and immune regulation in pinealectomy mice https://www.sciencedirect.com/science/article/pii/S002432051...

Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats https://pubmed.ncbi.nlm.nih.gov/14672618/ *This is significant because one of the side effects of chemotherapy is increased NFkB, which can induce to tumor growth/resistance*

Melatonin-mediated downregulation of thymidylate synthase as a novel mechanism for overcoming 5-fluorouracil associated chemoresistance in colorectal cancer cells https://academic.oup.com/carcin/article/40/3/422/5257709

Melatonin enhances sensitivity to fluorouracil in oesophageal squamous cell carcinoma through inhibition of Erk and Akt pathway https://www.nature.com/articles/cddis2016330

Melatonin inhibits AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK and activates caspase/Cyto C signaling to enhance the antitumor activity of berberine in lung cancer cells https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823085/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123278

>> Melatonin exhibited various mechanisms to restrain metastasis, such as modulation of cell–cell and cell–matrix interaction, extracellular matrix remodeling by matrix metalloproteinases, readjustment of the cytoskeleton, epithelial-mesenchymal transition, and angiogenesis [127]. A recent study reported that the overexpression of the ADAMTS family in renal cell carcinoma was suppressed by melatonin via amplifying of miR-let-7f/miR-181d and reducing protein stability. It is of note that ADAMTS, a disintegrin, and metalloprotease with thrombospondin motifs family, thought to have an impact on cell metastasis and developing of cancer stages.

Note:

>> Melatonin has short plasma half-life, variable oral absorption, and low variable bioavailability that could be due to extensive first pass metabolism [327], in addition to its poor solubility and stability [328]. Therefore, conventional oral dosage forms (immediate release) are unsuitable candidates for melatonin delivery.

Jokes on the cancer, I barely get any sleep

You’re killing it

Wait till you hear that <insert some disease here> is correlated with more waking hours.

Thanks for the info. I'm never sleeping again.

Welcome to life on Elm Street.

You’re body will betray you.

Now read an article about the negative effects of not getting enough sleep.

Running is good for your health

Running can cause knee issues

My general lay-person understanding is that your immune system is less active when you sleep. While I hate the way we tend to overlook other elements of the immune system and act like white blood cells are your entire immune system, in this case it may be very pertinent because white blood cells travel in the blood.

They may basically be going out into the blood when there are fewer white blood cells roaming the corridors, looking to kill something.

“Wake up” is a stretch, we have no idea what is going on here. Would be good to see how people’s circadian rhythms and sleep quality affected this process, maybe the cancer cells are being disposed of by the body during sleep and that process is disregulated. Fascinating research but I think getting to any real understanding from this is a way off.

So.. pretty much we can't rely on existing mechanisms in our bodies to defeat cancer. Obviously.. we need to find damaged cells, remove them, and replace them with undamaged cells. Likely we need to do this on a continuous basis.

Not human bodies, no. But look at other long lived species like elephants, who rarely get cancer and have even more cells than we do.

Just splice the right snippet of elephant DNA into ours to kill cancer for good.

Your immune system is continuously monitoring the body for cancerous cells. Each of us have probably had A cancerous cell hundreds of times. In order for the cancer to continue to grow, though, it needs a constellation of mutations to impede the immune response, among other things. Essentially, it's a race between a proto-tumor accreting more mutations, and the immune system finding and destroying it.

If we can figure out why this occurs during sleep, maybe we can trick cancer cells into thinking the patients are awake all the time (without actually affecting sleep wellness).

That’s unintuitive as hell, but of course Evolution doesn’t feel the need to construct things in a way that makes sense.

Not so unintuitive if you have seen enough molecular biology. A lot of cancers are the result of key cogs in the cellular / tissue growth machinery going crazy. A lot of tissue remodeling and growth happens while you sleep. So cancer cells going into turbo mode when you go to sleep doesn’t seem all that crazy.

Thank you, I learned something today already

> To do this, the team grafted breast cancer tumours into mice

Speaking of sleep, if I was doing the above I'm not sure I'd ever sleep well again.

"I never sleep, 'cause sleep is the cousin of death." - Nas

obligatory Young Ones reference:

https://www.youtube.com/watch?v=KEITpehWiXk

Or slightly more obscure, Jane Aumonier [1] from Alastair Reynolds' book The Prefect, who ends up with a mysterious scarab device attached to her spine that will kill her if she falls asleep, so she has to be kept medically awake for 11 years.

[1]: https://revelationspace.fandom.com/wiki/Jane_Aumonier

Little buggers.

Didn't know this journal does clickbait

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