C

BETA BLOCKERS, STRESS, AND BREAST CANCER:

Miriam Chiamaka OkonkwoThe North Carolina School of Science and Mathematics

Studying Alternative Cancer Treatments in Mouse Mammary Cells

Breast Cancer• In 2015,• Breast cancer estimated to be diagnosed in

over 200,000 US women• Over 40,000 US women died from breast

cancer

• Cancer treatments invasive• Looking for alternative treatments

(American Cancer Society 2015)http://www.nationalbreastcancer.org/breast-cancer-treatment

Beta-adrenergic pathway • Beta-adrenergic pathway binds stress hormones to beta receptors

• Cancer cells have beta receptors and use pathway to cause cancerous activities

Adapted from Cole and Sood 2013

Effect of Beta Blockers• Beta blockers are cardiovascular drugs• Inhibit binding of stress

hormones to beta receptors

•May inhibit cancerous activities of cancer cells

Adapted from Cole and Sood 2013

Methods• Cultured two cell lines• HC11 Mammary Mouse

Epithelium• JC Mouse Mammary

Adenocarcinoma

• Drug solutions diluted in media and then added to 6-well plate

Preliminary Experiments• Dosage experiments testing three different dosages of both the beta blocker and norepinephrine• Cells treated for 3 days before counting• Final concentrations• 100 µM beta blocker • 10 µM norepinephrine

Response Variables• Destructive sampling- 3 cell plates for each treatment; establish growth rate• Cells counted in hemocytometer stained for dead cells

cancerous

normal

H1: Cancerous Cell Type vs. Normal Cell TypeGr

owth

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e Ov

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Day

s high

low

norepinephrinecontrol

H1: Norepinephrine Treatment vs. ControlGr

owth

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s high

low

beta blocker

control

H1: Beta Blocker vs. ControlGr

owth

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Day

shigh

low

control

H1: All Possible Treatments vs. ControlGr

owth

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shigh

low

beta blockercancerous

norepinephrine

CRESULTS

Conclusion• Cell type• Higher % dead cells in cancerous than noncancerous

• Norepinephrine• No statistically significant effect on cells in growth rate or % death• Trend toward higher growth rate and lower % death

Implications for Beta Blocker• Beta blockers• Increase in % dead cells in cancerous cells, but decrease in

noncancerous cells

Future Work• Production of stress hormones in-vivo vs. administration of stress hormones as a drug in-vitro• Use different types of beta blockers/stress hormones• Cardioselective vs. noncardioselective (beta blockers)• Epinephrine vs. norepinephrine (stress hormones)

AcknowledgmentsDr. Amy SheckMs. GravesDr. Michael BrunoDr. Kim MonahanDr. Julian ParrisDr. Zermeena MarshallGlaxo Endowment to the North Carolina School of Science and MathematicsResearch in Biology Classes of 2016 and 2017

Dian Niu 2016

CQUESTIONS?

Literature CitedAmerican Cancer Society. 2014. What are the key statistics about breast cancer?.

http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics. Accessed 3/20/2015.

Barron, A., N. Zaman, G. Cole, R. Wensel, D. Okonko, and D. Francis. 2013. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information. International Journal of Cardiology 168: 3572-2579.

Giorgi, V., S. Gandini, M. Grazzini, S. Benemei, N. Marchionni, and P. Geppetti. 2013. Effect of beta-blockers and other antihypertensive drugs on the risk of melanoma recurrence and death. Mayo Clin Proc. 88: 1196-1203.

Marcotte, R., H. Smith, V. Sanquin-Genreau, R. McDonough, and W. Muller. 2011. Mammary epithelial-specific disruption of c-Src impairs cell-cycle progression and tumorigenesis. PNAS. 109: 2808-2813.

Wrobel, L. and F. Le Gal. 2014. Inhibition of human melanoma growth by a non-cardioselective beta blocker. Journal of Investigative Dermatology 135: 525-531.