Signal networks involved in the development of cancer stem cells’ phenotype: role of adapter proteins and design of nanomaterials-based anticancer therapy

Work number - M 26 FILED

Authors: Pasichnyk G.V., Horak I.R., Franskevich D.V.

 Presented by the Palladin Institute of Biochemistry of NAS of Ukraine

The serious of scientific works devoted to the research of adapter protein Ruk/CIN85 contribution to the formation and maintenance of the phenotype of cancer stem cells (CSCs) and the impact of nanomaterials (fullerene C₆₀) on the functioning of cells transformed with the prospect of further development of anticancer drugs.

A number of fundamental results on the adapter protein Ruk/CIN85 involvement in the process of carcinogenesis were obtained. In particular, it was found the increase of Ruk/CIN85 expression in human thyroid and breast primary tumors. It was shown that Ruk/CIN85 overexpression in breast adenocarcinoma cells and adrenal pheochromocytoma cells was accompanied by increased manifestation of number molecular features of CSCs. It was found that Ruk/CIN85 involved in migration and invasion of breast adenocarcinoma cells. Together, the data obtained indicate that this adapter protein may serve as prognostic tumor marker and potential target for development of pharmacological agents directed action.

It was demonstrated that carbon nanostructures fullerene C₆₀ is non toxic and can inhibit the production of reactive oxygen species caused by anticancer drug cisplatin in normal lymphoid cells. Fullerene C₆₀ is efficiently absorbed by leukemic cells and after photoexcitation it can induce apoptotic death by increased production of reactive oxygen species, increasing the concentration of Ca²⁺ in the cytosol, activation of p38 kinase, the decrease of mitochondrial potential and release of cytochrome c from mitochondria. For the first time it was shown that combined effect of photoexcited C₆₀ and cisplatin reduced the toxic concentrations of cisplatin and increased sensitivity to cisplatin-resistant leukemic cells.

The data obtained show that the study of cancer stem cells’ signaling networks to find potential markers and targets for therapy and directed effect on them by drugs developed on the basis of new nanomaterials will increase the effectiveness of traditional cancer treatment.

Number of publications: 53, including 1 monograph, 9 articles (3 – in journals with non-zero impact factor), 43 abstracts in the Proceedings of Ukrainian and international conferences. Works cited by 4 scientific journals (according to Scopus database), h-index is 1.