IN VITRO ANTINEOPLASTIC AND ANTICANCER STEM CELL EFFECTS OF CANNABIDIOL ISOLATED AND COMBINED WITH TRADITIONAL CHEMOTHERAPY (DOXORUBICIN) IN BREAST CARCINOMA OF THE HER2-ENRICHED MOLECULAR SUBTYPE

• Grant number: 24/04807-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: André Almeida Schenka
• Grantee: Anna Clara de Oliveira Martins
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Breast cancer is one of the main causes of death from malignant neoplasms in females worldwide and, for this reason, an important object of research involving the use of neoplastic stem cells (NSCs) as a primary pharmacological target. According to cumulative evidence, NSCs play a fundamental role in the development and maintenance of malignant neoplasms, especially in the face of therapeutic selective pressures. NSCs perform such functions thanks to their capacity for self-renewal, multilineage differentiation, low proliferative index and expression of transmembrane efflux transporters. Recent studies indicate that Cannabidiol (CBD), the most abundant non-psychotropic compound in Cannabis sativa, has antineoplastic effects (i.e., antiproliferative, antiangiogenesis and pro-apoptotic) in some solid tumors (lung cancer and glioblastoma, e.g.). In addition to these effects, CBD has low toxicity and alleviates other symptoms that may be related to malignant neoplasms, such as: emesis, pain, anxiety and depression. To date, there are few studies evaluating the potential of CBD as an antineoplastic agent (alone or combined with classic chemotherapy drugs) in the treatment of breast cancer or its effects on NSCs of this neoplasm (in particular, of the molecular subtype HER2 enriched). In this context, the present work aims to investigate the cytotoxic and anti-CTN effects of the drug CBD on cell lines of the luminal B1 (MCF7) and HER2-enriched (MGSO3 and SKBR3) subtypes. Cells from these lineages will be subjected to (1) control treatment (absence of drug), (2) isolated CBD, (3) isolated doxorubicin (standard/reference chemotherapy), or (4) a CBD/doxorubicin combination. The following parameters will be evaluated: concentration-response curve (using the MTT assay that assesses cell viability), cell proliferation (through immunocytochemical detection and ki67 quantification), apoptosis (through the Apoptag technique) and expression of classic NSC antigens (ALDH1 and CD133) by immunocytochemical method. We hope with this study to contribute to the characterization of the real antineoplastic/anti-CTNS role of CBD in human breast cancer, in particular of the HER2-enriched subtype (311 words). (AU)