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.
Results:
We show that loperamide and promethazine in doses of 80-100μg/ml exert oncocidal effects 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.
Targeting IKKε in androgen-independent prostate cancer causes phenotypic senescence and genomic instability
