Does Caffeic Acid Enhance the Antitumoral Response of Sorafenib on Hepatocellular Carcinoma? An In Vitro Approach.

• Grant number: 23/17585-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: May 31, 2025
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Guilherme Ribeiro Romualdo
• Grantee: Luana Riechelmann Casarin
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The hepatocellular carcinoma (HCC) is a malignant neoplasm of significant epidemiological burden with a poor prognosis. Current HCC therapies, including the universal tyrosine kinase inhibitor sorafenib (SOR), feature low efficacy. Thus, the potential synergy of bioactive compounds from foods, such as caffeic acid (CA), with traditional chemotherapy regimens is still encouraged in the literature, albeit underexplored. Within this context, the objective of this study is to assess whether exposure to CA enhances the antitumor effects of SOR using different in vitro approaches. Thus, human HCC cell line (C3A/HepG2) or activated hepatic stellate cells (LX2) will be individually exposed (two-dimensional model) with different concentrations of SOR (0, 3.12, 6.25, 12.5, 25, 50, 100, 200, 400, 800, and 1600 µM) or CA (0, 50, 100, 200, 400, 800, 1600, 3200, 6400, and 12800 µM) for 24 or 48 hours. Subsequently, the cell viability (MTT) and cytotoxicity (LDH) will be assessed, and the half-maximal effective concentration (EC50) of each will be calculated. Then, the drugs will be combined (1/2, 1/5, and 1/10 of the EC50 of SOR or CA) either equimolarly or by reducing SOR concentrations. Viability and cytotoxicity assays will be repeated, along with colony formation (C3A) and migration (LX2) assays. The drugs will also be tested in a three-dimensional spheroid model - co-culture of C3A/LX2 - when the EC50 of each compound (viability and cytotoxicity) will be assessed, and combinations will follow the strategy of the two-dimensional models.

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)

VALENTE, LETICIA CARDOSO; BACIL, GABRIEL PRATA; RIECHELMANN-CASARIN, LUANA; BARBOSA, GIULLIA CAVICHIOLLI; BARBISAN, LUIS FERNANDO; ROMUALDO, GUILHERME RIBEIRO. Exploring in vitro modeling in hepatocarcinogenesis research: morphological and molecular features and similarities to the corresponding human disease. Life Sciences, v. 351, p. 13-pg., 2024-06-13. (22/13402-9, 23/05411-0, 23/08751-7, 22/16633-1, 23/17585-3)

RIECHELMANN-CASARIN, LUANA; VALENTE, LETICIA CARDOSO; OTTON, ROSEMARI; BARBISAN, LUIS FERNANDO; ROMUALDO, GUILHERME RIBEIRO. Are glyphosate or glyphosate-based herbicides linked to metabolic dysfunction-associated steatotic liver disease (MASLD)? The weight of current evidence. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, v. 116, p. 21-pg., 2025-05-05. (22/06082-8, 23/05411-0, 23/08751-7, 23/17585-3)

VALENTE, LETICIA CARDOSO; RIECHELMANN-CASARIN, LUANA; OTTON, ROSEMARI; DELELLA, FLAVIA KARINA; BARBISAN, LUIS FERNANDO; ROMUALDO, GUILHERME RIBEIRO. Transcriptomic implications of low herbicide concentrations in hepatic cells: Insights into the individual and combined effects of 2,4-D, glyphosate, and AMPA. Toxicology Letters, v. 409, p. 11-pg., 2025-06-01. (22/06082-8, 23/05411-0, 23/08751-7, 23/17585-3)