A pinboard by
Reham Atteya

PhD Student, Zewail City of Science and Technology


Investigating mechanisms to enhance the efficacy and reduce cardiotoxicity of doxorubicin

Anthracyclines are a class of cancer chemotherapeutics considered to be one of the most efficacious anti-tumor drugs ever developed. Doxorubicin is one of the first anthracyclines to be discovered where today, it is widely used clinically for several solid and liquid tumors. Doxorubicin is the first line treatment for breast cancer and also used for soft tissue sarcomas and aggressive lymphomas. The anti-tumorogenic properties of doxorubicin stems from targeting Topoisomerase II (TOP2); an essential cellular enzyme that is required for regulating DNA topology during various cellular processes such as transcription, replication and recombination. Chronic cardiomyopathy and congestive heart failure have been strongly associated with doxorubicin treatment. Since compounds of natural origin present a rich territory for drug discovery, we set out to identify putative natural compounds with the view to mitigate or minimize doxorubicin cardiotoxicity. We identified harmine as a potentiator of cell death induced by non-toxic doses of doxorubicin on breast cancer cell lines in addition to a doxorubicin-resistant breast cancer cell line. Moreover, we have confirmed that the harmine-doxorubicin combination is not toxic on cardiomyocytes. These observations suggest that harmine may offer a new therapeutic opportunity to suppress doxorubicin’s dose-dependent cardiotoxicity. Currently, we aim to unveil the mechanism behind this synergistic activity and characterize whether this synergism would hold in vivo in a mouse tumor model.