leukotriene-b4 and Glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) drugs, such as Afatinib. However, clinically relevant drug-resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti-inflammatory effects analyzing p65/NF-κB and Leukotriene B4 expression and production of interleukins and growth factors (IL-8, IL-6, vascular endothelial growth factor, CXCL-12, and MMP-9). Considering the cardiotoxicity of TMZ and anti-EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti-inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti-inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies.

Topics: Afatinib; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Boswellia; Cardiotonic Agents; Cell Line, Tumor; Chemokine CXCL12; ErbB Receptors; Glioblastoma; Humans; Interleukin-6; Interleukin-8; Leukotriene B4; Lipid Peroxidation; Myocytes, Cardiac; Reactive Oxygen Species; Temozolomide; Transcription Factor RelA; Triterpenes