Department of Applied Chemistry and Chemical Engineering
&
Director, Central Science Lab
University of Rajshahi, Bangladesh

Title of the Invited Talk: Repurposing Eltrombopag Olamine: A Computational and Experimental Study on Its Anticancer Potential Against Breast and Hepatocellular Carcinoma

Abstract: Cancer treatment faces significant global challenges, highlighting the need for more effective therapeutic options. This study utilized computational screening of 1500 FDA-approved drugs via molecular docking, identifying eltrombopag olamine as a promising anticancer agent targeting GATA2, EGFR, FAS, TNFα, and TP53. Widely recognized for its ability to enhance platelet levels, eltrombopag olamine demonstrated potent in vitro anticancer activity against human breast (MCF-7) and hepatocellular carcinoma (SMMC-7721) cell lines, with IC 50 values of 31 µg/ml and 154 µg/ml, respectively. The observed antiproliferative effects were attributed to apoptosis, as confirmed by Hoechst 33342 staining and FITC-annexin V/PI assays, which revealed early and late apoptotic events. The involvement of caspase-3, -8, and -9 in the apoptotic mechanism was further validated using specific caspase inhibitors. Flow cytometry analysis indicated S-phase cell cycle arrest in both cell lines following eltrombopag
olamine treatment. Gene expression analysis through real-time PCR revealed upregulation of FAS, p53, Bax, TNFα, and cytochrome-C, alongside downregulation of ERK in MCF-7 cells. Similarly, in SMMC-7721 cells, TNFα, p53, and Bax were upregulated, while STAT3, MAPK, Notch1, PARP, EGFR, and ERK expression levels were reduced. These results suggest that eltrombopag-induced apoptosis involves multiple signaling pathways, including intrinsic, EGFR-MAPK-ERK, WNT, and death receptor pathways. Collectively, these findings underscore the potential of repurposing eltrombopag olamine as a novel therapeutic option for breast and hepatocellular carcinoma.