Bee Venom Induces Unfolded Protein Response in A172 Glioblastoma Cell Line

Abstract

Background: Glioblastoma is a type of brain tumor with poor response to available therapies, and shows high rate of mortality. Despite remarkable advancements in our knowledge about cytogenetic and pathophysiologic features of glioblastoma, current treatment strategies are mainly based on cytotoxic drugs; however, these therapeutic approaches are facing progressive failure because of the resistant nature of glioblastomas. In the recent years, however, promising results have emerged owing to targeted therapies toward molecular pathways within cancerous cells. Unfolded Protein Response (UPR) is a remarkable signaling pathway that triggers both apoptosis and survival pathways within cells, and therefore induces UPR-related apoptotic pathways in cancer cells by ER stress inducers. Objectives: Recently, the role of Bee venom (Bv), which contains powerful bioactive peptides, in inducing UPR-related apoptosis was revealed in cancer cell lines. Nevertheless, currently there are no reports of Bv potential ability in induction of UPR apoptotic routes in glioblastoma. The aim of current study was to evaluate possible role of Bee venome in inducing of UPR pathway within A172 glioblastoma cell line. Materials and Methods: We treated the A172 glioblastoma cell line with different Bv doses, and assessed UPR-related genes expression by real-time Polymerase Chain Reaction (PCR). Results: The IC50 of Bv for the studied cell line was 28 μg/mL. Furthermore, we observed that Bv can induce UPR target genes (Grp94 and Gadd153) over-expression through a dose-dependent mechanism. Conclusions: Our results suggest the potential role of Bv as a therapeutic agent for glioblastomas.

BCR-ABL promotes hematopoietic stem and progenitor cell formation in embryonic stem cells

“…4D and E). These observations support the idea that HSCL correspond to immature hematopoietic cells and unravel the activation of several stress pathways which have been shown to be misregulated in CML/AML LSCs, such as autophagy 48 , mitophagy 49 and UPR 50,51 .…”

Melittin as an Activator of the Autophagy and Unfolded Protein Response Pathways in Colorectal HCT116 Cell Line

“…Also, Fan et al described that the melittin gene-transfected human osteosarcoma cell line (MG63) triggered UPR-mediated apoptosis through a significant increase in the XBP1 and CHOP proteins level [ 24 ] . Bazi and colleagues also reported BV as an activator of the UPR pathway and UPR-related apoptosis in the A172 glioblastoma cell line [ 25 ] . While some investigations have reported that melittin restricts the proliferation and promotes apoptosis in colon cancer cells [ 12 , 29 ] , the autophagy and UPR pathways have not been targeted so far in these cells.…”

“…The effect of the BV and its main constituent melittin on the autophagy and UPR pathways have been reported in different cancers such as osteosarcoma [ 24 ] , glioblastoma [ 25 ] , lung [ 26 ] , liver [ 27 ] , and cervix cancers [ 28 ] . In spite of various investigations on the role of melittin in the growth inhibition and apoptosis induction in colon cancer cells [ 12 , 29 ] , to the best of our knowledge, there is no report about the function of melittin in autophagy and UPR pathways in the mentioned cells.…”

Oxidative stress in leukemia and antioxidant treatment

“…ROS are expected to be the ideal targets for therapeutic intervention, for high ROS levels are particularly relevant to BCR/ ABL kinase inhibitor resistance. [4,43] Antioxidants that regulate the level of oxidative stress are the primary defense line to regulate the overall state of health. Ivermectin is a new anti-cancer drug targeted to mitochondria, which can selectively kill CML cells by inducing oxidative stress and mitochondrial dysfunction, being a promising candidate drug for the treatment of CML.…”

“…Therefore, researchers are actively looking for new drugs that can stimulate cell differentiation and induce apoptosis of acute leukemia and multiple myeloma cells. ROS are expected to be the ideal targets for therapeutic intervention, for high ROS levels are particularly relevant to BCR/ABL kinase inhibitor resistance [4,43] …”