Research experiment by Miriam Chiamaka Okonkwo discussing the effects of the beta blocker propranolol on breast cancer progression

1. C
BETA BLOCKERS, STRESS,
AND BREAST CANCER:
Miriam Chiamaka Okonkwo
The North Carolina School of Science and Mathematics
Studying Alternative Cancer Treatments in Mouse
Mammary Cells

2. 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

3. 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

4. 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

5. 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

6. 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

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

9. cancerous
normal
GrowthRateOver3Days
H1: Cancerous Cell Type vs. Normal Cell Type
high
low

10. norepinephrine
control
GrowthRateOver3Days H1: Norepinephrine Treatment vs. Control
high
low

11. beta blocker
control
GrowthRateOver3Days
H1: Beta Blocker vs. Control
high
low

12. control
GrowthRateOver3Days H1: All Possible Treatments vs. Control
high
low
beta blocker
cancerous
norepinephrine

13. CRESULTS

19. 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

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

21. 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)

22. Acknowledgments
Dr. Amy Sheck
Ms. Graves
Dr. Michael Bruno
Dr. Kim Monahan
Dr. Julian Parris
Dr. Zermeena Marshall
Glaxo Endowment to the North Carolina School of Science and Mathematics
Research in Biology Classes of 2016 and 2017
Dian Niu 2016

23. CQUESTIONS?

24. Literature Cited
American 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.