DUGiDocsStudy of the anticancer activity of a nuclear directed HP-RNase variant and different metal-based compounds
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Cancer is the leading cause of death due to non-communicable diseases worldwide. Despite the advances in the development of new antitumor drugs, there are still problems such as the resistance that tumor cells acquire against them, as well as the serious side effects observed after their application. In this thesis, three new families of compounds have been studied as possible antitumor drugs. The first one, a ribonuclease called NLSPE5 that has been modified by protein engineering, and the other two are metallic compounds based on manganese (Mn) and iron (Fe).
The results obtained indicate that NLSPE5, in addition to altering the epigenetic pattern of the tumor cell lines, decrease their capacity to migrate and invade nearby tissues. On the other hand, the results of the investigation of the new Mn-based compounds show that, of all of them, Mn8 has a strong antitumor effect on lung and ovarian tumor cell lines. This effect is similar to that observed with commercial antitumor drugs such as Cis-platinum. The results also indicate that Mn8 breaks the DNA of the cancer cells in presence of reactive oxygen species. It was also observed that this compound causes cell death by apoptosis.
Finally, the results of the study of Fe-based compounds show that all of them are highly cytotoxic against lung and ovarian tumor lines, and as well as Mn8, these compounds break DNA in presence of reactive oxygen species. Among the different Fe-based compounds, compound 10 showed the highest selectivity for tumor lines. Moreover, this compound induces apoptosis and reduces the migration capacity of a cancer cells. In conclusion, all the investigated compounds are very promising as antitumor drugs
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