Estrogen Receptor Activation By Tobacco Smoke Condensate In Hormonal Therapy-resistant Breast Cancer

Lucenzo01

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May 17, 2016
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347
It seems that Peat is right again.

Abstract

The relationship between tobacco smoke and breast cancer incidence has been studied for many years, but the effect of smoking on hormonal therapy has not been previously reported. We investigated the effect of smoking on hormonal therapy by performing in vitro experiments. We first prepared tobacco smoke condensate (TSC) and examined its effect on estrogen receptor (ER) activity. The ER activity was analyzed using MCF-7-E10 cells into which the estrogen-responsive element (ERE)-green fluorescent protein (GFP) reporter gene had been stably introduced (GFP assay) and performing an ERE-luciferase assay. TSC significantly activated ERs, and upregulated its endogenous target genes. This activation was inhibited by fulvestrant but more weakly by tamoxifen. These results suggest that the activation mechanism may be different from that for estrogen. Furthermore, using E10 estrogen depletion-resistant cells (EDR cells) established as a hormonal therapy-resistant model showing estrogen-independent ER activity, ER activation and induction of ER target genes were significantly higher following TSC treatment than by estradiol (E2). These responses were much higher than those of the parental E10 cells. In addition, the phosphorylation status of signaling factors (ERK1/2, Akt) and ER in the E10-EDR cells treated with TSC increased. The gene expression profile induced by estrogenic effects of TSC was characterized by microarray analysis. The findings suggested that TSC activates ER by both ligand-dependent and -independent mechanisms. Although TSC constituents will be metabolized in vivo, breast cancer tissues might be exposed for a long period along with hormonal therapy. Tobacco smoke may have a possibility to interfere with hormonal therapy for breast cancer, which may have important implications for the management of therapy.
 
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Brace for RPF smoking apologists attack
 

biffbelvin

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Jul 3, 2017
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Brace for RPF smoking apologists attack

Smoking cessation was such a positive experience for me that I can't help be baffled by such views.

It can give quite a bit of perspective on other topics on this forum as i think it's easy to fall into a reductive approach and miss the forest for the trees.

For further reference; i smoked between 3-7 rolls a day for 7 years, with maybe 6 months of 'missed days' and attempts to stop woven in there.
 

Filip1993

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Joined
Nov 7, 2013
Messages
280
Smoking cessation was such a positive experience for me that I can't help be baffled by such views.

It can give quite a bit of perspective on other topics on this forum as i think it's easy to fall into a reductive approach and miss the forest for the trees.

For further reference; i smoked between 3-7 rolls a day for 7 years, with maybe 6 months of 'missed days' and attempts to stop woven in there.

How did smoking cessation affect you? I'm trying to quit smoking at the moment.
 

Energizer

Member
Joined
Mar 3, 2013
Messages
492
It seems that Peat is right again.

Abstract

The relationship between tobacco smoke and breast cancer incidence has been studied for many years, but the effect of smoking on hormonal therapy has not been previously reported. We investigated the effect of smoking on hormonal therapy by performing in vitro experiments. We first prepared tobacco smoke condensate (TSC) and examined its effect on estrogen receptor (ER) activity. The ER activity was analyzed using MCF-7-E10 cells into which the estrogen-responsive element (ERE)-green fluorescent protein (GFP) reporter gene had been stably introduced (GFP assay) and performing an ERE-luciferase assay. TSC significantly activated ERs, and upregulated its endogenous target genes. This activation was inhibited by fulvestrant but more weakly by tamoxifen. These results suggest that the activation mechanism may be different from that for estrogen. Furthermore, using E10 estrogen depletion-resistant cells (EDR cells) established as a hormonal therapy-resistant model showing estrogen-independent ER activity, ER activation and induction of ER target genes were significantly higher following TSC treatment than by estradiol (E2). These responses were much higher than those of the parental E10 cells. In addition, the phosphorylation status of signaling factors (ERK1/2, Akt) and ER in the E10-EDR cells treated with TSC increased. The gene expression profile induced by estrogenic effects of TSC was characterized by microarray analysis. The findings suggested that TSC activates ER by both ligand-dependent and -independent mechanisms. Although TSC constituents will be metabolized in vivo, breast cancer tissues might be exposed for a long period along with hormonal therapy. Tobacco smoke may have a possibility to interfere with hormonal therapy for breast cancer, which may have important implications for the management of therapy.

Even if they show that TCS is somehow causing "ER" activation in an in vitro cell line of MCF-7-E10 it's a bit of a leap itself to assume that means tobacco smoking raises estrogen across the board, at least that's my interpretation. Though that doesn't imply tobacco smoke doesn't increase estrogen, just that I'm not seeing that conclusion following here. The most definitive evidence that would persuade me that tobacco smoke increases estrogen would be to expose animals to it and take some blood samples and compare them to sham-smoke controls. As far as I've seen and stated in other threads, those such animals lived longer than non-smoking controls ironically (by about 20%). I've also seen research that indicates tobacco smoking is associated with a 3-fold lower risk of osteoarthritis in women, increases DHEA and testosterone, and I wouldn't be surprised if it dramatically lowers estrogen since it is so highly androgenic. In fact the study on women smokers below corrobates that. I am not as sure about the other study (since they didn't measure estrogen), but I still included it since it is notable that smoking increases androgens (presumably, this should give pause to the notion that smoking is highly estrogenic, since androgens and estrogens are virtually the opposite hormonal processes. and although estrogen can be synthesized from testosterone via aromatase, nicotine itself inhibits aromatase, which is probably a major factor in the estrogen lowering effect and androgenic effect in tobacco smoke (though not the singular one).

The antiestrogenic effect of cigarette smoking in women


The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men
 
Last edited:

Lucenzo01

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Even if they show that TCS is somehow causing "ER" activation in an in vitro cell line of MCF-7-E10 it's a bit of a leap itself to assume that means tobacco smoking raises estrogen across the board, at least that's my interpretation. Though that doesn't imply tobacco smoke doesn't increase estrogen, just that I'm not seeing that conclusion following here. The most definitive evidence that would persuade me that tobacco smoke increases estrogen would be to expose animals to it and take some blood samples and compare them to sham-smoke controls. As far as I've seen and stated in other threads, those such animals lived longer than non-smoking controls ironically (by about 20%). I've also seen research that indicates tobacco smoking is associated with a 3-fold lower risk of osteoarthritis in women, increases DHEA and testosterone, and I wouldn't be surprised if it dramatically lowers estrogen since it is so highly androgenic. In fact the study on women smokers below corrobates that. I am not as sure about the other study (since they didn't measure estrogen), but I still included it since it is notable that smoking increases androgens (presumably, this should give pause to the notion that smoking is highly estrogenic, since androgens and estrogens are virtually the opposite hormonal processes. and although estrogen can be synthesized from testosterone via aromatase, nicotine itself inhibits aromatase, which is probably a major factor in the estrogen lowering effect and androgenic effect in tobacco smoke (though not the singular one).

The antiestrogenic effect of cigarette smoking in women


The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men

Blood levels of hormones are tricky. Maybe the estrogen went to the tissues?
 
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biffbelvin

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Jul 3, 2017
Messages
154
How did smoking cessation affect you? I'm trying to quit smoking at the moment.

I tried and failed a number of times to quit myself. I found reading Allen Carr helped divorce the romanticism with smoking that i'd built up over the years. I also just told myself to pretend that a craving was actually a need for food. I started smoking at an incredibly stressful time of my life, when i didn't have enough money to properly feed myself, so i figured that appetite suppression was a big part of my habit.

First 3 days sucked. I was anxious, irritable, depressive and I was getting stomach cramps and bloating but i stuck by it. Whenever i got a really bad craving i would 'treat' myself to some food (regardless of how peaty it was). 5 days in, the stomach cramps where gone and i felt like i could 'breathe' more, but i did have chest pains for a couple more days which was concerning. By 3 weeks however, the cravings were weak and manageable and i didn't have any negative symptoms that i could attribute to smoking. At 3 months my cravings where gone and i was totally comfortable with never smoking again.

Below are the improvements to my health that i experienced as a result of quitting smoking:
  • Better taste and smell
  • Easier to fall asleep, better sleep quality and waking in a much less irritable/anti-social mood
  • Less aches and pains from better sleep and oxygenation (used to have chronic pain in wrists/neck).
  • More resilient to stress and stressful situations, more accepting of personal responsibility, less manic
  • Much greater tolerance/enjoyment of exercise
  • Improved discipline and adaptability of daily routine
  • Greater sensitivity to blood sugar levels (this technically sucks, but i figure 5 years of more smoking would have had me sleep-walking into some sort of diabetic/metabolic disease)

I must admit however that in the absence of smoking, i became overly sensitive to the effects of alcohol. Halfway through one drink and I can already feel my vision blurring, breathing getting worse etc. As a knock-on effect, this sometimes increases my social anxiety in these sorts of situations, if i'm not with old friends or familiar places. Eating food helps ease me back to normal though, so i imagine it's a blood sugar thing (and was probably underlying beforehand).

edit: full disclosure, smoking a couple of cigarettes when out drinking helps blunt the negative effects of drinking for me. I figure it's not such a bad thing since i do this every other month at most.
 
Last edited:

Filip1993

Member
Joined
Nov 7, 2013
Messages
280
I tried and failed a number of times to quit myself. I found reading Allen Carr helped divorce the romanticism with smoking that i'd built up over the years. I also just told myself to pretend that a craving was actually a need for food. I started smoking at an incredibly stressful time of my life, when i didn't have enough money to properly feed myself, so i figured that appetite suppression was a big part of my habit.

First 3 days sucked. I was anxious, irritable, depressive and I was getting stomach cramps and bloating but i stuck by it. Whenever i got a really bad craving i would 'treat' myself to some food (regardless of how peaty it was). 5 days in, the stomach cramps where gone and i felt like i could 'breathe' more, but i did have chest pains for a couple more days which was concerning. By 3 weeks however, the cravings were weak and manageable and i didn't have any negative symptoms that i could attribute to smoking. At 3 months my cravings where gone and i was totally comfortable with never smoking again.

Below are the improvements to my health that i experienced as a result of quitting smoking:
  • Better taste and smell
  • Easier to fall asleep, better sleep quality and waking in a much less irritable/anti-social mood
  • Less aches and pains from better sleep and oxygenation (used to have chronic pain in wrists/neck).
  • More resilient to stress and stressful situations, more accepting of personal responsibility, less manic
  • Much greater tolerance/enjoyment of exercise
  • Improved discipline and adaptability of daily routine
  • Greater sensitivity to blood sugar levels (this technically sucks, but i figure 5 years of more smoking would have had me sleep-walking into some sort of diabetic/metabolic disease)

I must admit however that in the absence of smoking, i became overly sensitive to the effects of alcohol. Halfway through one drink and I can already feel my vision blurring, breathing getting worse etc. As a knock-on effect, this sometimes increases my social anxiety in these sorts of situations, if i'm not with old friends or familiar places. Eating food helps ease me back to normal though, so i imagine it's a blood sugar thing (and was probably underlying beforehand).

Thanks for your answer!
 
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