The antiproliferative and apoptotic effects of apigenin on glioblastoma cells

Abstract

Objectives Glioblastoma (GBM) is highly proliferative, infiltrative, malignant and the most deadly form of brain tumour. The epidermal growth factor receptor (EGFR) is overexpressed, amplified and mutated in GBM and has been shown to play key and important roles in the proliferation, growth and survival of this tumour. The goal of our study was to investigate the antiproliferative, apoptotic and molecular effects of apigenin in GBM. Methods Proliferation and viability tests were carried out using the trypan blue exclusion, MTT and lactate dehydrogenase (LDH) assays. Flow cytometry was used to examine the effects of apigenin on the cell cycle check-points. In addition, we determined the effects of apigenin on EGFR-mediated signalling pathways by Western blot analyses. Key findings Our results showed that apigenin reduced cell viability and proliferation in a dose-and time-dependent manner while increasing cytotoxicity in GBM cells. Treatment with apigenin-induced is poly ADP-ribose polymerase (PARP) cleavage and caused cell cycle arrest at the G2M checkpoint. Furthermore, our data revealed that apigenin inhibited EGFR-mediated phosphorylation of mitogen-activated protein kinase (MAPK), AKT and mammalian target of rapamycin (mTOR) signalling pathways and attenuated the expression of Bcl-xL. Conclusion Our results demonstrated that apigenin has potent inhibitory effects on pathways involved in GBM proliferation and survival and could potentially be used as a therapeutic agent for GBM.

Apigenin from Croton betulaster Müll restores the immune profile of microglia against glioma cells

“…Other studies have also showed that apigenin is able to inhibit glioblastoma cell proliferation, induce its differentiation and apoptosis (Coelho et al, ; Stump et al, ), and decrease the expression of pro‐angiogenic factors like VEGF and TGFβ‐1 (Freitas et al, ) and inhibits glioblastoma stem cells (Kim, Jung, Lee, Sohng, & Jung, ). On the other hand, we have demonstrated here and in our previous studies that apigenin at the same apigenin concentration is not toxic to microglia and astrocytes (Coelho et al, ; Stump et al, ).…”

“…Cardenas, Marder, Blank, and Roguin (2006) reported in their in vitro research that the flavonoid apigenin inhibited the proliferation and viability of breast cancer, melanoma, uterine cervix, and adenocarcinoma cells. Previous studies, with the use of apigenin and others flavonoids, have demonstrated the antiproliferative and apoptotic effects on glioblastoma cells (Stump et al, 2017) and antitumoral and immunomodulatory potential in C6 glioma cell line, in terms of cytotoxicity, inhibition of migration, and regulation of trophic factors that reduced tumor growth and migration with similar results in co-cultures microglia/glioma cells (Coelho et al, 2016;da Silva et al, 2019). Other studies have also showed that apigenin is able to inhibit glioblastoma cell proliferation, induce its differentiation and apoptosis (Coelho et al, 2015;Stump et al, 2017), and decrease the expression of pro-angiogenic factors like VEGF and TGFβ-1 (Freitas et al, 2010) and inhibits glioblastoma stem cells (Kim, Jung, Lee, Sohng, & Jung, 2016).…”

“…Previous studies, with the use of apigenin and others flavonoids, have demonstrated the antiproliferative and apoptotic effects on glioblastoma cells (Stump et al, 2017) and antitumoral and immunomodulatory potential in C6 glioma cell line, in terms of cytotoxicity, inhibition of migration, and regulation of trophic factors that reduced tumor growth and migration with similar results in co-cultures microglia/glioma cells (Coelho et al, 2016;da Silva et al, 2019). Other studies have also showed that apigenin is able to inhibit glioblastoma cell proliferation, induce its differentiation and apoptosis (Coelho et al, 2015;Stump et al, 2017), and decrease the expression of pro-angiogenic factors like VEGF and TGFβ-1 (Freitas et al, 2010) and inhibits glioblastoma stem cells (Kim, Jung, Lee, Sohng, & Jung, 2016). On the other hand, we have demonstrated here and in our previous studies that apigenin at the same apigenin concentration is not toxic to microglia and astrocytes (Coelho et al, 2016;Stump et al, 2017).…”

“…plant, the apigenin, also demonstrated an antiglioma effect, being glioma cells sensitive to apigenin than were to normal astrocytes. Studies demonstrated that treatment of glioma cells with apigenin resulted in the reduction of viability and migration, differentiation of the remaining viable cells, as well as the secretion of inflammatory cytokines, and apoptosis (Coelho et al, ; Stump et al, ).…”

“…Studies demonstrated that treatment of glioma cells with apigenin resulted in the reduction of viability and migration, differentiation of the remaining viable cells, as well as the secretion of inflammatory cytokines, and apoptosis (Coelho et al, 2016;Stump et al, 2017).…”