euroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastom

Author(s):Show less -

do Nascimento, Ravena Pereira ^[1] ; dos Santos, Balbino Lino ^{[1, 2]} ; Amparo, Jessika Alves Oliveira ^[1] ; Soares, Janaina Ribeiro Pereira ^[1] ; da Silva, Karina Costa ^[1] ; Santana, Monique Reis ^[1] ; Almeida, Aurea Maria Alves Nunes ^[1] ; da Silva, Victor Diogenes Amaral ^[1] ; Costa, Maria de Fatima Dias ^{[1, 3]} ; Ulrich, Henning ^[4] ; Moura-Neto, Vivaldo ^{[4, 3, 5, 6]} ; Lopes, Giselle Pinto de Faria ^[7] ; Costa, Silvia Lima ^{[1, 3]}

Affiliation

^[1] Univ Fed Bahia, Inst Hlth Sci, Dept Biochem & Biophys, Lab Neurochem & Cell Biol, BR-40110902 Salvador, BA - Brazil

^[2] Fed Univ Vale Sao Francisco, Acad Coll Nurse, Dept Hlth, BR-56304205 Petrolina, Pernambuco - Brazil

^[3] Natl Inst Translat Neurosci INCT CNPq INNT, BR-21941902 Rio De Janeiro, RJ - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo, SP - Brazil

^[5] Univ Fed Rio de Janeiro, Inst Biomed Sci, BR-21941902 Rio De Janeiro, RJ - Brazil

^[6] Paulo Niemeyer State Inst Brain, BR-20230024 Rio De Janeiro, RJ - Brazil

^[7] Admiral Paulo Moreira Inst Sea Studies IEAPM, Dept Marine Biotechnol, BR-28930000 Arraial Do Cabo, RJ - Brazil

• Document type: Journal article
• Source: PHARMACEUTICS; v. 14, n. 1 JAN 2022.
• Web of Science Citations: 0

Abstract

Glioblastomas (GBMs) are tumors that have a high ability to migrate, invade and proliferate in the healthy tissue, what greatly impairs their treatment. These characteristics are associated with the complex microenvironment, formed by the perivascular niche, which is also composed of several stromal cells including astrocytes, microglia, fibroblasts, pericytes and endothelial cells, supporting tumor progression. Further microglia and macrophages associated with GBMs infiltrate the tumor. These innate immune cells are meant to participate in tumor surveillance and eradication, but they become compromised by GBM cells and exploited in the process. In this review we discuss the context of the GBM microenvironment together with the actions of flavonoids, which have attracted scientific attention due to their pharmacological properties as possible anti-tumor agents. Flavonoids act on a variety of signaling pathways, counteracting the invasion process. Luteolin and rutin inhibit NF kappa B activation, reducing IL-6 production. Fisetin promotes tumor apoptosis, while inhibiting ADAM expression, reducing invasion. Naringenin reduces tumor invasion by down-regulating metalloproteinases expression. Apigenin and rutin induce apoptosis in C6 cells increasing TNF alpha, while decreasing IL-10 production, denoting a shift from the immunosuppressive Th2 to the Th1 profile. Overall, flavonoids should be further exploited for glioma therapy. (AU)

• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants