S132: In Vitro Analysis of Embelin in Combination with Tyrosine Kinase Inhibitors for Treating Breast Cancer
Poster Presenter
Jassam Alsiyaghy
PharmD Candidate
Chicago State University United States
Objectives
To evaluate the effect of EGFR inhibitors, HH antagonist and embelin (XIAP
inhibitor) alone or in combination on proliferation, apoptosis and migration of breast cancer cells
in a time and dose fashion.
Method
Antiproliferative effect was assessed using MTT assay, apoptosis determined using
flow cytometry and pipette tip was used to create parallel wound for the assessment of cell
migration in breast cancer cells.
Results
The antiproliferative effect of embelin was dose dependent at lower concentrations but
not time dependent with IC50 values of0.55, 0.61, 0.56 at 24, 48 and 72 hrs. The antiproliferative
effect of EGFR inhibitors were both dose and time dependent with afatinib being more potent
than gefitinib and IC50 values of 0.81, 0.56, 0.55 and 2.00, 1.80, 0.71 respectively at 24, 48 and
72 hrs. Cyclopamine inhibitory effect on MDA-MB-231 cell proliferation was dose but not time
dependent and was less potent than EGFR inhibitors and embelin. IC50 values were 1.63, 1.64
and 0.61 at 24, 48 and 72 hours. EGFR inhibitors were observed to reduce endogenous
expression of XIAP. Afatinib was more potent in inducing apoptosis than gefitinib and both were
more potent in inducing apoptosis than cyclopamine. However, combination of afatinib and
embelin significantly reduced the expression of XIAP and induced greater apoptotic effect than
combination of either therapy with gefitinib or cyclopamine.
Conclusion
Embelin is found to have more antiproliferative effect than EGFR inhibitors with
afatinib being more potent than gefitinib and both more effective in inhibiting MDA-MB-231
cell proliferation than Hedgehog inhibitor (Cyclopamine). Additionally, combination therapy
more effectively induced apoptosis and inhibited breast cancer cell migration.
