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Human cancer represents a significant public health problem not only in Brazil but also worldwide. It is known that cancer, especially in advanced stages, is refractory to the most commonly available therapeutic approaches, such as chemotherapy, radiotherapy and immunotherapy. The modulation of autophagy has been investigated as a promising antitumor therapeutic approach, whose efforts in preclinical research have propelled several studies. Autophagy (or macroautophagy) is a highly conserved catabolic process in eukaryotes that plays a vital role in cell metabolism, signaling, immunity, longevity, development and differentiation. Autophagy is a changeable process for drugs and therefore represents an attractive target for the development of new therapeutic interventions against human cancers, especially those refractory to chemotherapy. In this sense, studies aimed to modulate autophagy with therapeutic implications attend to the demand for innovative antitumor strategies. The Nobel Prize for Physiology or Medicine of 2016 for autophagy testifies to its growing importance in human health. In order to contribute in this scenario Waleska Martins et al., by studying the biomolecules isomeric, the pentacyclic triterpenoids betulinic acid (BA) and oleanolic (AO), as well as phenothiazine photosensitizers, methylene blue (MB) and 1,9 dimethyl methylene blue (DMMB), have established that the state of efficiency of pro-survival mitofagia depends intrinsically on lysosomal homeostasis, and to induce effective cell death, it is just to promote parallel damage in mitochondrial and lysosomal membranes. As demonstrated for triterpenoids, the photoinduced damage by Photodynamic Therapy (PDT) also closely associated with the activation of pro-survival autophagy, in which loss of lysosomal function shifts pro-autophagy to pro-death. By applying molecular and cellular biotechnological tools, it will be possible to better understand the state of the art of membrane damage related to autophagic impairment. For this, we intend to evaluate synthetic membrane mimetics, for example multilamellar liposomes and giant unilamellar vesicles (GUVs), in addition to biological membranes (organelles and erythrocytes). Conceivably, all the scientific production generated in this Project will help in the rational design of new biotechnological processes for target organelle therapies, in which autophagy acts mechanistically as a pro-death process. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARTINS, WALESKA K.; BELOTTO, RENATA; SILVA, MARYANA N.; GRASSO, DANIEL; SURIANI, MAYNNE D.; LAVOR, TAYNA S.; ITRI, ROSANGELA; BAPTISTA, MAURICIO S.; TSUBONE, TAYANA M. Autophagy Regulation and Photodynamic Therapy: Insights to Improve Outcomes of Cancer Treatment. FRONTIERS IN ONCOLOGY, v. 10, JAN 20 2021. Web of Science Citations: 0.
TSUBONE, TAYANA MAZIN; MARTINS, WALESKA KERLLEN; FRANCO, MARCIA S. F.; SILVA, MARYANA N.; ITRI, ROSANGELA; BAPTISTA, MAURICIO S. Cellular compartments challenged by membrane photo-oxidation. Archives of Biochemistry and Biophysics, v. 697, JAN 15 2021. Web of Science Citations: 1.
TONOLLI, PAULO N.; MARTINS, WALESKA K.; JUNQUEIRA, HELENA C.; SILVA, MARYANA N.; SEVERINO, DIVINOMAR; SANTACRUZ-PEREZ, CAROLINA; WATANABE, I; BAPTISTA, MAURICIO S. Lipofuscin in keratinocytes: Production, properties, and consequences of the photosensitization with visible light. Free Radical Biology and Medicine, v. 160, p. 277-292, NOV 20 2020. Web of Science Citations: 1.

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