MODULATION OF BIOCHEMICAL AND PHOTOCHEMICAL PARALLEL DAMAGES: IMPLICATIONS ON PRO-SURVIVAL AUTOPHAGY

• Grant number: 18/23257-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2019
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Biophysics
• Principal Investigator: Waleska Kerllen Martins Gardesani
• Grantee: Maryana do Nascimento da Silva
• Host Institution: Centro Universitário Anhanguera de São Paulo. São Bernardo do Campo , SP, Brazil

Abstract

Human cancer represents a significant public health problem worldwide. As a strategy to reverse this reality, the modulation of autophagy as an antitumor approach has been investigated. Depending on the context, such as tumor type and staging, both activating agents and autophagy inhibitors have antitumor action. Similarly, Photodynamic Therapy (PDT) has been highlighted as a modulator of pro-survival autophagy. By comparative analysis using human non-malignant and malignant cells, we intend to promote extrinsic cellular stresses in which pro-survival autophagy can be modulated to cell death by suppressing lysosomal function. By using technologic tools in cellular and molecular biology, we intend to modulate autophagy after treatment with the pentacyclic triterpenoids betulinic acid (BA) and oleanolic acid (OA) parallel or not to the photodamege promoted by PDT using as photosensitizers (PSs) the phenothiazine compounds methylene blue (MB) and 1,9-dimethyl-methylene blue (DMMB). Comparative analysis regarding the PDT efficency using theses PSs and according to the presence or absence of parallel mitochondrial (OA) or mitochondrial / lysosomal (BA) membrane damage may contribute to the understanding of the concept of lysosomal damage and its impact on the role of pro-survival autophagy. Thus, by expanding this model in the near future, it will be possible to subsidize new scientific developments in biotechnological innovation, in order to consolidate the public interest in promoting an improvement in the survival of cancer patients.

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

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. (18/23257-0, 18/22922-0, 13/07937-8)

MARTINS, WALESKA KERLLEN; TSUBONE, TAYANA MAZIN; SANCHES, CHIMARA EMILIA NASCIMENTO; ROCHA, CLEIDIANE DE SOUSA; NAVARRO, RICARDO SCARPARO; STOLF, BEATRIZ SIMONSEN; DINIZ, SUSANA NOGUEIRA; ITRI, ROSANGELA; BAPTISTA, MAURICIO S.. Modulation of Autophagy by Ursolic and Betulinic Acids: Distinct Cytotoxic and Membrane-Disruption in Malignant and Nonmalignant Cells. Cell Biology International, v. 49, n. 11, p. 19-pg., 2025-08-23. (16/07642-6, 12/50680-5, 18/23257-0, 13/07937-8, 18/22922-0)

CHIARELLI-NETO, ORLANDO; GARCEZ, MICHELLE LIMA; PAVANI, CHRISTIANE; MARTINS, WALESKA; CASTRO, FERNANDA CRISTINA DE ABREU QUINTELA; AMBROSIO, ROBERTA PASSAMANI; MEOTTI, FLAVIA CARLA; BAPTISTA, MAURICIO S.. Inflammatory stimulus worsens the effects of UV-A exposure on J774 cells. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 239, p. 9-pg., 2023-01-10. (18/22922-0, 13/07937-8, 18/23257-0)