Can Chronic Stress Cause Cancer ?
Posted on November 4 2016
Chronic Stress – Nervous Breakdown and Catatonia
The classic 1949 war movie, “Twelve Oclock High” starring Gregory Peck, reveals the effect of
chronic stress on B-17 pilots during the war. After many weeks of stressful daylight bombing
raids, Gregory Peck suffers a nervous breakdown, and is carried away in a catatonic state. I was
impressed with this brutally honest depiction of the effects of chronic stress in war time. (left
image courtesy of Bantam Books)
Chronic Stress is a Bad Thing
Chronic stress is undoubtedly a bad thing because of release of massive adrenal hormones called
catecholamines. This is extremely deleterious to our immune system, increases susceptibility to
viral infection and delays wound healing. (1-2) Chronic stress has been implicated in
cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, gastric ulcer, as well as cancer (2)
Can Chronic Stress Cause Cancer ?
This leads us to the main question of the article, can chronic stress cause cancer? Let’s examine
an animal model of chronic stress to answer this question.
Animal Model of Chronic Stress
The animal model of chronic stress involves restraining mice in narrow tubes for a few hours
every day. To make matters worse, the mice may be immersed in cold water.
Left image Schematic Showing Mouse retrained in narrow tube. This is restraint stress. Courtesy
of Zhang et al. “Restraint Stress Causes Acute Gastric Injury In Mice: ” Scientific reports 6
(2016).
Does Chronic Stress Causes Cancer ?
Dr Donald Lamkin used a lymphoblastic leukemia model in mice undergoing restraint stress to
answer the question, does chronic stress cause cancer?(3) Dr Lamkin’s 2012 study published in
Brain Behavior showed that mice suffering from restraint stress (Red Ellipse in below image) had
accelerated progression of cancer compared to controls (Green Ellipse).
Beta-Blockers Block Effect of Stress
The effect of stress was abrogated by giving the mice a Beta-Blocker drug called propranolol,
which blocks the activation of the sympathetic nervous system. (see image below). The
Propranolol treated mice actually showed regression of cancer compared to controls. Thus
proving that beta-adrenergic stimulation drives cancer growth, and by blocking the effect of
chronic stress with a beta blocker drug, we can slow the progression of cancer..
Fig 3 B Betaadrenergic signaling in stress-enhanced Acute Lymphoblastic Leukemia progression. Mice were
injected with cancer cells tagged with fluorescent marker (blue spots)Green Ellipse shows
control mice NO STRESS, injected with cancer cells. Red Ellipse shows STRESSED mice with
increased cancer growth compared to controls. Propranolol treated mice (Beta Blocker) had
actual regression of cancer compared to controls. Courtesy of Lamkin, Donald M., et al. (3)
How does stress produces Beta-Adrenergic nervous system stimulation?
Chronic stress stimulates the adrenal medulla to secrete massive amounts of the catecholamines,
epinephrine and norepinephrine. These stress hormones stimulate the Beta Adrenergic receptors
in the nervous system, as well as in cancer cells.
Mobile cancer cells will frequently migrate to the adrenal glands, seeking the adrenal medulla
which secretes high concentration of catecholamines thus causing large adrenal masses. See
image below.
Adrenal Metastatic Disease is Quite Common
Above Image: Adrenal lymphoma on CAT scan. (left image a) Both Adrenals are replaced by
large masses (white arrows) (Right image b) shows bulky retro-peritoneal nodal masses with
renal invasion (black arrows) Courtesy of Indian Journal of Endocrinology and Metabolism
. 2015 Volume 19 Issue 1 P16-24 Adrenal imaging (Part 2): Medullary and secondary adrenal
lesions by Ekta et al.
Modifying Diet to Down Regulate the Sympathetic Nervous System
In addition to the use of Beta Blocker Drugs, the sympathetic nervous system can be down
regulated by dietary interventions as advocated by Nicholas Gonzalez MD as a part of his cancer
treatment protocol.(19-22).
Conclusion: Chronic Stress is unhealthy because it releases catecholamines which activate the
Sympathetic Nervous system. Cancer cells are sensitive to beta adrenergic stimulation caused by
chronic stress. This stimulates cancer cell growth.
Articles with Related Interest: Adrenal Fatigue
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314
954-792-4663
Links and References
free pdf
1) Glaser, Ronald, and Janice K. Kiecolt-Glaser. “Stress-induced immune dysfunction:
implications for health.” Nature Reviews Immunology 5.3 (2005): 243-251. stress-inducedimmune-dysfunction-implications-for-health-nature-reviews-immunology-2005-glaser-ronald
2) Reiche, Edna Maria Vissoci, Sandra Odebrecht Vargas Nunes, and Helena Kaminami
Morimoto. “Stress, depression, the immune system, and cancer.” The lancet oncology 5.10
(2004): 617-625.stress-depression-the-immune-system-cancer-lancet-oncology-reiche-ednamaria-2004
stress promotes cancer – Nice flourescent mouse images
3) Lamkin, Donald M., et al. “Chronic stress enhances progression of acute lymphoblastic
leukemia via ß-adrenergic signaling.” Brain, behavior, and immunity 26.4 (2012): 635-641.
Clinical studies suggest that stress-related biobehavioral factors can accelerate the progression of
hematopoietic cancers such as acute lymphoblastic leukemia (ALL), but it is unclear whether
such effects are causal or what biological pathways mediate such effects. Given the network of
sympathetic nervous system (SNS) fibers that innervates the bone marrow to regulate normal
(non-leukemic) hematopoietic progenitor cells, we tested the possibility that stress-induced SNS
signaling might also affect ALL progression. In an orthotopic mouse model, Nalm-6 human preB ALL cells were transduced with the luciferase gene for longitudinal bioluminescent imaging
and injected i.v. into male SCID mice for bone marrow engraftment. Two weeks of daily restraint
stress significantly enhanced ALL tumor burden and dissemination in comparison to controls, and
this effect was blocked by the ß-adrenergic antagonist, propranolol. Although Nalm-6 ALL cells
expressed mRNA for ß1- and ß3-adrenergic receptors, they showed no evidence of cAMP
signaling in response to norepinephrine, and norepinephrine failed to enhance Nalm-6
proliferation in vitro. These results show that chronic stress can accelerate the progression of
human pre-B ALL tumor load via a ß-adrenergic signaling pathway that likely involves indirect
regulation of ALL biology via alterations in the function of other host cell types such as immune
cells or the bone marrow microenvironment.
Chronic restraint stress significantly enhanced pre-B ALL tumor burden and dissemination in a
well-established mouse xenograft model of the most prevalent form of human pediatric leukemia.
Pharmacologic inhibition studies showed that stress effects were mediated by ß-adrenergic
signaling in vivo
Mechanistic investigations have documented a key role of ß-adrenergic signaling in mediating
stress effects on progression of several types of solid tumor (Sloan et al., 2010; Stefanski & BenEliyahu, 1996; Thaker et al., 2006).
the present results raise the possibility that cancer-related anxiety might contribute to disease
recurrence and that pharmacologic inhibition of such effects at the level of the ß-adrenergic
receptor may represent an effective strategy for managing those effects in patients with preB ALL who are in remission or still have active disease.