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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
Rat
e Ov
er 3
Day
s high
low
norepinephrinecontrol
H1: Norepinephrine Treatment vs. ControlGr
owth
Rat
e Ov
er 3
Day
s high
low
beta blocker
control
H1: Beta Blocker vs. ControlGr
owth
Rat
e Ov
er 3
Day
shigh
low
control
H1: All Possible Treatments vs. ControlGr
owth
Rat
e Ov
er 3
Day
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.