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Novell filr cedarville5/20/2023 ![]() It has been shown that luteolin’s antiproliferative property is due to its ability to arrest the cell cycle at checkpoints, G1/s, and G2/M ( Lin et al., 2008). Flavonoids display various beneficial effects such as antioxidant, anticancer, anti-inflammatory, and antiviral properties. Flavonoids are some of the most abundant compounds found in the human diet ( Sharma et al., 2011). Luteolin ( Figure 1B) is a common flavonoid found in various plants, fruits, vegetables, and medicinal herbs. (B) Chemical structure of luteolin, a flavonoid derived from vegetable sources. ![]() (A) Chemical structure of erlotinib, a small molecule inhibitor of EGFR. As erlotinib is clinically approved for other indications, enhancing its efficacy with the right adjuvants will increase its effectiveness and utility in treating GBM.Ĭhemical structures of erlotinib and luteolin. Resistance to erlotinib appears to be linked to EGFR vIII suppression in extrachromosomal DNA ( Haas-Kogan et al., 2005 Padfield et al., 2015). It shows promise in treating gliomas ( Clarke et al., 2014 Raizer et al., 2016). Erlotinib ( Figure 1A), is an EGFR tyrosine kinase inhibitor that prevents intracellular phosphorylation of EGFR in cancer cells, preventing downstream signaling and causing cancer cell death ( Haas-Kogan et al., 2005). Due to poorly understood mechanisms, the heterogeneity of the tumor can allow the cells to reversibly increase or decrease their level of EGFR vIII expression, maximizing their growth potential ( Haas-Kogan et al., 2005 Padfield et al., 2015). The EGFR overexpression contributes to the highly proliferative and treatment-resistant nature of this tumor. There is an abnormal expression of EGFR in 40–60 percent of patients with GBM. The epidermal growth factor receptor (EGFR) is an important factor in GBM since growth factors and their receptors are primarily responsible for regulating cell proliferation ( Padfield et al., 2015). The most common treatments are surgical removal of tumors, radiation therapy, and/or chemotherapy using temozolomide, an alkylating agent ( Friedman et al., 2000). GBM is a heterogeneous tumor, which means that every cell within the tumor exhibits different characteristics, making treatment challenging. Low survival rates, decreased apoptosis, increased proliferation, and cell migration are some of the hallmarks of glioblastoma. ![]() Patients’ survival rates are low, with the average survival time after diagnosis being approximately 14 months ( Krex et al., 2007). GBM presents with a poor prognosis of about 37% in 1 year and 5-year survival of 5% ( Krex et al., 2007 Tan et al., 2018). Among all primary brain tumors, GBMs account for 10–15 percent of all glial tumors. The glioblastoma multiforme grade IV (GBM) is a malignant tumor that affects ten out of every 100,000 adults each year ( Iacob and Dinca 2009 Siegel et al., 2021). These findings suggest that combining luteolin with erlotinib offers a potential treatment strategy for glioblastoma multiforme IV. In addition, the combination of luteolin and erlotinib reduced the phosphorylation of downstream EGFR cell signaling molecules such as Akt, NF kappa B, and STAT3 in a concentration-dependent manner. In a concentration-dependent fashion, the combination of luteolin and erlotinib reduced cell proliferation ( p < 0.05) and induced apoptosis by cleaving PARP and increasing caspase expression. ![]() We investigated the combined effects of erlotinib and luteolin on proliferation and apoptosis on glioblastoma cell lines overexpressing EGFR or glioma cells expressing truncated EGFR (ΔEGFR). Luteolin, a natural flavonoid, inhibits cell growth and induces apoptosis in cancer cells. Several clinical trials have explored a combination of erlotinib with other agents to treat glioblastoma since it is believed that erlotinib would benefit patients with GBM with EGFR mutations or expression. It is FDA approved to treat a variety of EGFR-mediated cancers. A small molecule called erlotinib inhibits EGFR receptors by binding to their adenosine triphosphate (ATP) binding sites. Increased expression of EGFR leads to increased proliferation, decreased apoptosis, and increased resistance to chemotherapeutic agents. The epidermal growth factor (EGFR) receptor is frequently overexpressed in glioblastoma multiforme IV (GBM).
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