Non-specific beta-blocker, Propranolol, may reduce cancer risk and stress hormone-induced cancer progression providing increases in survival times for patients with certain cancers such breast, prostate, lung, ovarian and others; A REVIEW.
What are beta-blockers?
Beta-blockers are cheap, well known drugs prescribed for hypertension (high blood pressure), migraines, glaucoma and for arrhythmia (irregular heart beat).
How do beta-blockers work?
Beta-blockers are also called beta-adrenergic blocking agents and work by blocking receptors for the stress hormones adrenaline (epinephrine) and noradrenaline (nor-epinephrine), and thus calming the heart beat and reducing blood pressure.
There are receptors in other tissues and beta-blocker drugs fall into three categories, specific for the heart, and ‘non-specific’ for other organs and tissues. It is the non-specific beta-blockers that have most effect with cancer.
Beta 1 receptors are found in the heart and kidneys.
Beta 2 receptors are found in the lungs, liver, uterus, skeletal muscle, smooth muscle and gastrointestinal tract.
Beta 3 receptors are found in fat cells.
N.B. Beta-blockers are not without their side-effects and you should consult with your doctor before taking them.
Why might Beta-blockers have a role in cancer?
Chris Woollams, former Oxford University Biochemist writes, “It’s not cancer that kills you, it’s metastasis (cancer spread). And that’s the goal for many researchers – stopping metastases. Stress is a big biochemical factor in promoting and driving metastasis.
For example, 2019 research from the University of Basel has shown that an increase in stress hormones in breast cancer causes an increase in glucocorticoid receptors in distant organs in the body, and that both are linked to higher levels of metastasis. Worse, the distant receptors can even modify the cancer, making the new tumours less receptive to the drugs.
UCLA have a Stress Management Laboratory specialising in cancer and they have proven that people who actively manage their stress – and stress hormone levels – survive longer. They have been using natural ways to do this – recommendations include counseling, a colourful Mediterranean Diet, taking fish oils, exercise and especially yoga, and meditation. This is because certain anti-inflammatory foods along with the production of endorphins and opioids can neutralise the effects of stress hormones.
Beta-blockers can also stop or greatly reduce the effects of stress hormones in cancer. However, many patients fear their side-effects. Not surprisingly, some patients prefer natural alternatives. We know that the Ayurvedic herb Ashwagandha is an adaptogen and can neutralise stress hormones. We also know that Theanine from green tea can reduce stress, anxiety and both cancer risk and progression.
So, is there actually research on Beta-blockers - and specifically Propranolol - decreasing cancer risk and increasing cancer survival? As you will see, I think that there's not much research for beta blockers as a class of drugs, but there is some research for the non-specific beta blocker Propranolol with some cancers. Although in honesty, the research results are a little mixed."
Can Propranolol reduce cancer risk?
In a population study of almost 25,000 people in Taiwan (1), a cohort of those taking Propranolol was matched with a group not taking it. The study showed that taking propranolol for more than a thousand days can significantly reduce the risk of head and neck, esophagus, stomach, colon, and prostate cancers.
Propranolol may have several very different actions. For example several studies have shown it's potential to block angiogenesis. For example, in one study (2) Propranolol was shown to inhibit angiogenesis by down-regulating the expression of vascular endothelial growth factor (VEGF). The National Cancer Institute is covering a clinical trial (3) with Kaposi Sarcoma because of this property.
Breast Cancer and beta-blockers
The Basel study was not the first with breast cancer. In 2012, researchers from Vanderbilt Center for Bone Biology showed in mice (4) that stress hormones had the ability to make bones more receptive to cancer. Dr. Florent Elefteriou demonstrated that stress hormones provoke a typical ‘fight or flight’ activation of the sympathetic nervous system and that this primed the bones. Stress hormones are proven to remodel the bone structure anyway, and this same mechanism creates a more favourable environment for the cancer to attack. Currently drugs such as Denosumab attempt to strengthen bones against attack.
Evidence from the Vanderbilt cancer clinic supported this. People whose cancer and/or treatment had made them stressed or depressed had shorter survival times. Since both stress and depression activate the sympathetic nervous system, Elefteriou’s team injected mice with fluorescent breast cancer cells, then used a drug that mimics sympathetic system stress activation. Sure enough, the cancer cells moved towards the bones as soon as stress hormones were heightened; a molecule dubbed RANKL known to break down bones was more prevalent in the bones, and more lesions were found.
The researchers then went on to show that a beta-blocker called Propranolol could block this effect.
In a 2017 study on stress-induced metastatic breast cancer progression to the lungs (5) the researchers suggested both Propranolol and Salbutamol would be effective at limiting this effect.
Ovarian Cancer and beta-blockers
In a retrospective study (6), researchers from MD Anderson showed that women with ovarian cancer who were taking beta-blockers during their chemotherapy, lived on average more than four years longer than those who were not. The type of beta-blocker was however important. Those who took cardiovascular beta-blockers (Beta1), showed a modest gain in survival from 40 to 42 months on average. However, this who took a non-selective beta-blocker (Beta2 and Beta3), the median overall survival climbed from 38 months to 95 months.
An overview (7) on the work of Professor Anil Sood with gynaecological cancers it concludes that stress hormones actually prevent ovarian cancer cells from breakdown and destruction. Noradrenaline actually prevents cancer cells from death, whilst stimulating metastasis, the formation of new blood supplies and mobility and invasion of tissues. Stress actually promotes cancer cells to leave the primary tumour, and Sood has shown that stress can promote Vascular Endothelial Growth Factor (VEGF) while Beta-blockers can stop this.
Sood also argues that more general Beta 2 and Beta 3 blockers offered better outcomes than specific Beta 1 blockers and that this fact was causing confusion in research results. In mice where tumours grew and spread more quickly under the effects of stress hormones, the effect can be blocked by the non-specific Propranolol.
Lung cancer and beta blockers
In another retrospective MD Anderson study, this time of 722 patients having radiotherapy with non-small cell lung cancer, both less metastases and an increase in survival times were noted (8).
Colorectal cancer and beta-blockers
A study of beta blocker use in Germany did not support the use of beta blockers reducing Colorectal cancer risk (9).
In a Swedish study of 22 337 patients where 36.1% were prescribed preoperative beta-blockers, survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and having more health issues (10).
As you will have seem, most research relates to human use and population studies, often pre-2018. A 2021 study in the laboratory looked at propranolol use with gastric cancer cells (11). The study concluded that propranolol inhibited the proliferation of gastric cancer cells by inducing G1-phase cell cycle arrest and apoptosis.
Improving cancer survival with beta-blockers? A summary
Certainly the type of beta-blocker seems important. Frankly there is not much research to support beta blockers as a class of drugs providing significant advantages in reducing risk and increasing survival across all cancer types. It's the non-specific (i.e. not for specific cardiovascular/blood pressure issues) beta-blocker Propranolol that seems the drug of choice for several cancers.
In a meta-review (12) of beta-blockers showing effect by cancer type, Propranolol is referenced as offering reduction of tumour progression and increases in survival times for multiple cancers such as breast cancer, ovarian cancer, lung cancer, pancreatic cancer, melanoma, prostate cancer, stomach cancer, leukaemia, angiosarcoma and nasopharynx cancer.
Don't forget though that beta blockers do have their own side-effects. Typically, common side effects include cold hands or feet, extreme tiredness, weight gain, dizziness, and trouble sleeping. Less common side effects can include depression and shortness of breath.
We hope this review provided both information and balance.
Go to: Repurposing old drugs to fight cancer
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Ref:
- Propranolol reduces cancer risk - Ping-Ying Chang et al; Medicine (Baltimore). 2015 Jul 13;94(27)
- Propranolol inhibits angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell; Ling Zhang et al; Int J Clin Exp Pathol. 2013 Dec 15;7(1):48–55.
- Propranolol for the Treatment of Adult Patients with Kaposi Sarcoma; Clinical Trial; NCI
- VU study finds stress fuels breast cancer metastasis to bone - http://news.vumc.org/2012/07/18/stress-breast-cancer-metastasis/
- The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB- 231 Cell Line;Ezequiel Mariano Rivero et al; Cancer Drug Targets; 2017;17(8):756-766
- Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer - Jack L Watkins, et al; 24 August 2015; American Cancer Society
- Betting on Beta Blockers; MD Anderson - https://www.mdanderson.org/publications/conquest/betting-on-beta-blockers.h34-1589046.html
- Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy; H M Wang et al; Ann Oncol. 2013 May;24(5):1312-9.
- Beta blocker use and colorectal cancer risk: population-based case-control study; Lina Jansen et al; Cancer 2012 Aug 15;118(16):3911-9
- Effects of beta-blocker therapy on mortality after elective colon cancer surgery: a Swedish nationwide cohort study; Rebecka Ahl et al; BMJ Open. 2020 Jul 7;10(7)
- Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis; Gastric Cancer. 2021 Sep;24(5):1037-1049.
- Meta analysis of the effects of beta blocker on survival time in cancer patients; Chel Hun Choi et al; Clinical Oncology
Published: 27 March 2014, Volume 140, pages 1179–1188, (2014)
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