Antineoplastic and anti-cancer stem cell effects of cannabidiol in Burkitt lymphoma cell lines

• Grant number: 24/03837-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2024
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: André Almeida Schenka
• Grantee: Helena Alves Freire dos Santos
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Introduction: Burkitt lymphoma (BL) is a highly aggressive, though potentially curable, form of non-Hodgkin lymphoma. Despite achieving high cure rates in developed countries (90% among children and 60% among adults), it is associated with low survival in low-income countries (45% in Uganda, e.g.). Several chemotherapy regimens have been described, however, all contain drugs with significant systemic toxicity. Recent studies indicate that Cannabidiol (CBD) 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 in the treatment of BL or its effects on tumor stem cells (TSCs) in this particular neoplasm and others. TSCs constitute a cellular subpopulation of malignant neoplasms with the capacity for self-renewal, multilineage differentiation and resistance to multiple therapeutic modalities, playing an important role in late relapses. Rationale: it is important to search for new therapeutic strategies for BL that are curative (especially for economically disadvantaged populations), have low toxicity and act on tumor stem cells (TSC). Aim: to verify the antineoplastic and anti-CTT actions of CBD in LB, in an in vitro context. Materials and methods: cells from 4 immortalized LB lines (Daudi, Raji, Namalwa and Ramos cell lines) will be cultivated in vitro and subjected to (1) control treatment (culture medium only), or (2) with increasing concentrations of isolated CBD or (2) the reference drug (daunorubicin) for 72h to determine the respective IC50 concentrations of these drugs, using the classic MTT assay. In a subsequent experiment, cells from these lines will be cultured again and treated for 72h with CBD and DAU at their respective IC50 concentrations. At the end of this experiment, the cells will be evaluated for their proliferative index (using the ki67 immunocytochemical marker), apoptosis rate (using the Apoptag assay) and number of CTTs (using the CTT immunocytochemical marker, ALDH-1). Expected results: we hope to contribute to the characterization of the real antineoplastic/anti-CTT role of CBD.