The intensification of anticancer activity of LFM-A13 by erythropoietin as a possible option for inhibition of breast cancer

• Main Authors: Dariusz Rozkiewicz (Author), Justyna Magdalena Hermanowicz (Author), Anna Tankiewicz-Kwedlo (Author), Beata Sieklucka (Author), Krystyna Pawlak (Author), Robert Czarnomysy (Author), Krzysztof Bielawski (Author), Arkadiusz Surazynski (Author), Joanna Kalafut (Author), Alicja Przybyszewska (Author), Mariusz Koda (Author), Katarzyna Jakubowska (Author), Adolfo Rivero-Muller (Author), Dariusz Pawlak (Author)
• Format: Book
• Published: Taylor & Francis Group, 2020-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1475-6366; 1475-6374; 10.1080/14756366.2020.1818738
• Keywords: erythropoietin; lfm-a13; bruton's tyrosine kinase; breast cancer; zebrafish; Therapeutics. Pharmacology; RM1-950
• Source: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 35, Iss 1, Pp 1697-1711 (2020)

Recombinant human erythropoietin (Epo) is an effective and convenient treatment for cancer-related anaemia. In our study for the first time, we evaluated the effect of simultaneous use of Epo and Bruton's tyrosine kinase (BTK) inhibitor LFM-A13 on the viability and tumour development of breast cancer cells. The results demonstrated that Epo significantly intensifies the anticancer activity of LFM-A13 in MCF-7 and MDA-MB-231. The featured therapeutic scheme efficiently blocked the tumour development in zebrafish experimental cancer model. Epo and LFM-A13 administered together resulted in effective cell killing, accompanied by attenuation of the BTK signalling pathways, loss of mitochondrial membrane potential (MMP), accumulation of apoptotic breast cancer cells with externalised PS, a slight increase in phase G0/G1 and a reduction in cyclin D1 expression. Simultaneous use of Epo with LFM-A13 inhibited early stages of tumour progression. This therapeutic scheme may be rationale for further possible research.