Investigating the mechanism of action of Solanum lycocarpum glycoalkaloids free and encapsulated in nanoparticles: in vitro study and 3D cells platforms of bladder cancer and other cancer cells lines

• Grant number: 17/09025-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): June 29, 2017
• Effective date (End): June 28, 2018
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Mariza Abreu Miranda
• Supervisor: Mandip Singh Sachdeva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Florida Agricultural and Mechanical University (FAMU), United States
• Associated to the scholarship: 15/14665-0 - Development of functionalized nanoparticles with folate for the delivery of glycoalkaloids of Solanum lycocarpum and biological evaluation using 2D and 3D cell culture models, BP.PD

Abstract

Bladder cancer (BC) is the most common cancer of the urinary tract with an estimate of 401,000 new cases diagnosed annually worldwide. The current main therapies of BC have low effectiveness, high recurrence rate and several side effects. Glycoalkaloids (GAs) (solamargine and solasonine) are secondary metabolites found with high concentrations in Solanum lycocarpum fruits and the literature reports their potential cytotoxic effects against different tumor cell lines. Our preliminary tests with glycoalkaloids free and encapsulated in polymeric nanoparticles showed cytotoxic activity against RT4 bladder cancer cells through apoptosis and inhibiting their cycle cells in G2/M phase. Until now, these GAs have not been tested against bladder cancer cells. Therefore, it is interesting to explore the mechanisms by which these compounds free or encapsulated in nanoparticles exert their cytotoxic effect and to identify molecular signaling involved in their activities. Our investigations in Research Internships Abroad will include the identification of pathway markers of apoptosis and angiogenesis in RT4 cancer cells. Other goal is to add a fluorophore to the poly lactic acid (PLA) polymer in order to obtain fluorescent nanoparticles. With these nanoparticles, we will be able to perform other analyses such as cell uptake and confocal microscopy. Once that the GAs are reported as cytotoxic compounds to cancer cells, we also propose to screen their cytotoxicity (free and encapsulated form) in different 3D cultures models using bladder cancer cells and other cancer cells lines. These studies can help in understanding the action of GAs in cancer as well as giving the student a great background on 3D platforms, improving knowledge and expanding the research line of our research group in Brazil. (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)

MIRANDA, MARIZA ABREU; MARCATO, PRISCYLA DANIELY; MONDAL, ARINDAM; CHOWDHURY, NUSRAT; GEBEYEHU, ARAGAW; SURAPANENI, SUNIL KUMAR; LOPES BADRA BENTLEY, MARIA VITORIA; AMARAL, ROBSON; PAN, CHONG-XIAN; SINGH, MANDIP. Cytotoxic and chemosensitizing effects of glycoalkaloidic extract on 2D and 3D models using RT4 and patient derived xenografts bladder cancer cells. Materials Science & Engineering C-Materials for Biological Applications, v. 119, FEB 2021. (17/09025-7)