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Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines.
Anticancer Agents Med Chem. 2020; 20(8):1017-1027.AA

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 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.

Authors+Show Affiliations

Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.Dr. A.Q. Khan Institute of Biotechnology & Genetic Engineering, University of Karachi, Karachi, Pakistan.Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.Department of Surgery, Aga Khan University, Karachi, Pakistan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32271699

Citation

Baig, Abdul M., et al. "Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines." Anti-cancer Agents in Medicinal Chemistry, vol. 20, no. 8, 2020, pp. 1017-1027.
Baig AM, Rana Z, Mannan MM, et al. Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines. Anticancer Agents Med Chem. 2020;20(8):1017-1027.
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, 20(8), 1017-1027. https://doi.org/10.2174/1871520620666200409142239
Baig AM, et al. Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines. Anticancer Agents Med Chem. 2020;20(8):1017-1027. PubMed PMID: 32271699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Future Oncotargets: Targeting Overexpressed Conserved Protein Targets in Androgen Independent Prostate Cancer Cell Lines. AU - Baig,Abdul M, AU - Rana,Zohaib, AU - Mannan,Mohammad M, AU - Khaleeq,Areeba, AU - Nazim,Fizza, AU - Katyara,Preet, AU - Abbas,Farhat, PY - 2019/06/19/received PY - 2019/11/22/revised PY - 2020/01/14/accepted PY - 2020/4/10/pubmed PY - 2020/4/10/medline PY - 2020/4/10/entrez KW - DU145 KW - Microarray KW - PC3 KW - anti-cancer drugs KW - calmodulin KW - gene expression KW - prostate cancer KW - the oncomine SP - 1017 EP - 1027 JF - Anti-cancer agents in medicinal chemistry JO - Anticancer Agents Med Chem VL - 20 IS - 8 N2 - 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 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. SN - 1875-5992 UR - https://www.unboundmedicine.com/medline/citation/32271699/Future_Oncotargets:_Targeting_Overexpressed_Conserved_Protein_Targets_in_Androgen_Independent_Prostate_Cancer_Cell_Lines L2 - http://www.eurekaselect.com/180815/article DB - PRIME DP - Unbound Medicine ER -
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