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.