RESUMO
Cancer cells display high proliferation rates and survival provided by high glycolysis, chemoresistance and radioresistance, metabolic features that appear to be activated with malignancy, and seemed to have arisen as early in evolution as in unicellular/prokaryotic organisms. Based on these assumptions, we hypothesize that aggressive phenotypes found in malignant cells may be related to acquired unicellular behavior, launched within a tumor when viral and prokaryotic homologs are overexpressed performing likely robust functions. The ensemble of these expressed viral and prokaryotic close homologs in the proteome of a tumor tissue gives them advantage over normal cells. To assess the hypothesis validity, sequences of human proteins involved in apoptosis, energetic metabolism, cell mobility and adhesion, chemo- and radio-resistance were aligned to homologs present in other life forms, excluding all eukaryotes, using PSI-BLAST, with further corroboration from data available in the literature. The analysis revealed that selected sequences of proteins involved in apoptosis and tumor suppression (as p53 and pRB) scored non-significant (E-value>0.001) with prokaryotic homologs; on the other hand, human proteins involved in cellular chemo- and radio-resistance scored highly significant with prokaryotic and viral homologs (as catalase, E-value=zero). We inferred that such upregulated and/or functionally activated proteins in aggressive malignant cells represent a toolbox of modern human homologs evolved from a similar key set that have granted survival of ancient prokaryotes against extremely harsh environments. According to what has been discussed along this analysis, high mutation rates usually hit hotspots in important conserved protein domains, allowing uncontrolled expansion of more resistant, death-evading malignant clones. That is the case of point mutations in key viral proteins affording viruses escape to chemotherapy, and human homologs of such retroviral proteins (as Ras, Akt and EGFR) can elicit the same phenotype. Furthermore, a corollary to this hypothesis presumes that target-directed anti-cancer therapy should target human protein domains of low similarity to prokaryotic homologs for a well-succeeded anti-cancer therapy.
Assuntos
Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Genes Bacterianos/genética , Genes Neoplásicos/genética , Fenótipo , Células Procarióticas/química , Apoptose/genética , Adesão Celular/genética , Movimento Celular/genética , Biologia Computacional , Metabolismo Energético/genética , Humanos , Modelos Biológicos , Células Procarióticas/metabolismo , Alinhamento de Sequência , Homologia de SequênciaRESUMO
Alpinia zerumbet plantlets were cultured in vitro in MS medium supplemented with growth regulators, including IAA, TDZ and BAP. Using high performance liquid chromatography (HPLC), the production of rutin, kaempferol-3-O-glucuronide, and kaempferol-3-O-rutinoside was evaluated, based on leaf hydroalcoholic extracts of three-month-old plantlets. The relative concentration of phenolics from the hydroalcoholic extracts of plantlets cultured in control medium reached 100% compared with plantlets treated with growth regulators and donor plants (80%). The in vitro rutin production was more pronounced than the other flavonoids. While no direct relation between the content of phenolic compounds and increased flavonoid production was observed, the combination of IAA + TDZ enhanced the production of rutin (83.2 microg/g dried leaves) and kaempferol-3-O-glucuronide (29 microg/g dried leaves), compared with growth regulators used alone. Overall, these findings suggest the value of in vitro cultivation as a means of enriching phenolic and flavonoid production in medicinal plants.