A New Twist in Cellular Resistance to the Anticancer Drug Bleomycin-A5

Mustapha      Aouida; Dindial      Ramotar

Abstract

Bleomycin is a potent chemotherapeutic agent that can mediate cell killing by attacking the DNA. It is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas and squamous cell carcinomas of the cervix, head and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug for other types of cancers. Herein, we review recent findings from both yeast and human cells showing that uptake of bleomycin-A5 is a key mechanism that limits toxicity of the drug. We also discuss how the mammalian transporter hCT2 (SLC22A16) could be used to predict the outcome of tumor responses towards bleomycin therapy, and highlight the importance of further exploring this permease with respect to its regulation and pharmacological substrates for treating a wide range of cancers.

Keywords: Bleomycin, cancer cells, drug resistance, substrates, therapy, transport, Anticancer Drug, mammalian transporter hCT2, Streptomyces verticillis, guanine base, apurinic/apyrimidinic, antineoplastic agents, Saccharomyces cerevisiae, bleomycin hydrolase (BLH1), thiol protease specific inhibitor, Agp2, L-carnitine, fatty acid β-oxidation, acetyl-CoA, L-carnitine transporters, hCT2, OCTN2, RT-PCR, N1-acetylspermine, Jurkat cells, adriamycin, OCTN1, SLC22A4, SLC22A5, OCTN3, SLC22A21, OCT1, SLC22A1, OCT2, SLC22A2