Future oncotargets: Targeting overexpressed conserved protein targets in androgen independent prostate cancer cell lines

Authors

Abdul Mannan Baig, Aga Khan UniversityFollow
Zohaib Rana, Aga Khan UniversityFollow
Mohammad Mohsin Mannan, Dr. A.Q. Khan Institute of Biotechnology & Genetic Engineering, University of Karachi, Karachi. Pakistan
Areeba Khaleeq, Aga Khan UniversityFollow
Fizza Nazim, Aga Khan UniversityFollow
Preet Katyara, Aga Khan University
Farhat Abbas, Aga Khan UniversityFollow

Document Type

Article

Department

Biological and Biomedical Sciences; Surgery; Urology

Abstract

Background: Targeting evolutionarily conserved proteins in malignant cells and the adapter proteins involved in signalling that generates from such proteins may play a cardinal role in the selection of anti-cancer drugs. Drugs targeting these proteins could be of importance in developing anti-cancer drugs.
Objectives: We inferred that drugs like loperamide and promethazine that act as antagonists of proteins conserved in cancer cells like voltage-gated Calcium channels (Cav), Calmodulin (CaM) and drug efflux (ABCB1) pump may have the potential to be re-purposed as an anti-cancer agent in Prostate Cancer (PCa).
Methods: Growth and cytotoxic assays were performed by selecting loperamide and promethazine to target Cav, CaM and drug efflux (ABCB1) pumps to elucidate their effects on androgen-independent PC3 and DU145 PCa cell lines.
Result: We show that loperamide and promethazine in doses of 80- 100µg/ml exert oncocidal when tested in DU145 and PC3 cell lines. Diphenhydramine which shares its targets with promethazine, except the CaM, failed to exhibit oncocidal effects.
Conclusion: Anti-cancer effects can be of significance if structural analogues of loperamide and promethazine that specifically target Cav, CaM and ABCB1 drug efflux pumps can be synthesized or these two drugs could be re-purposed after human trials in PCa.

Comments

Volume, issue, and pagination are not provided by the author/publisher

Publication (Name of Journal)

Anti-Cancer Agents in Medicinal Chemistry

Recommended Citation

Baig, A. M., Rana, Z., Mannan, M. M., Khaleeq, A., Nazim, F., Katyara, P., Abbas, F. (2020). Future oncotargets: Targeting overexpressed conserved protein targets in androgen independent prostate cancer cell lines. Anti-Cancer Agents in Medicinal Chemistry.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_bbs/826