Therefore, we combined ITs (9.2.27-PE38KDEL or Mel-14-PE38KDEL) targeting chondroitin sulfate proteoglycan 4 (CSPG4) with a panel of Bcl-2 family inhibitors (ABT-737, ABT-263, ABT-199 [Venetoclax], A-1155463, and S63845) against patient-derived glioblastoma, melanoma, and breast cancer cells/cell lines.
Our data indicate that concomitant inhibition of RAC1 and Bcl-2/Bcl-xL induces pro-apoptotic and anti-migratory glioblastoma phenotypes as well as synergistic anti-neoplastic activities.
In this study, we examined whether inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL enhances the biological effects of the repurposed CUSP9 regimen in an in vitro setting of glioblastoma.
We analysed the transcript expression of CLEC5A in glioblastoma by accessing The Cancer Genome Atlas (TCGA). qRT-PCR was performed to detect the RNA expression of genes in cells and tissues, and Western blot was used to measure the protein levels (Cyclin D1, Bcl-2, BAX, PCNA, MMP2, MMP9, Akt and Akt phosphorylation) in tissues and cells.
Furthermore, the expression levels of the Bcl-2 anti-apoptotic protein was significantly decreased while Bax and caspase-3 expression were both increased in glioblastoma cells (all, p<0.05).
The inhibition of both SH-SY5Y and U87MG cell proliferation was associated with an increase in the thiosulfate level, the number of cells with the inactive form of Bcl-2 protein, and with a decrease of mitochondrial membrane potential.
MAO-B inhibitors selegiline and rasagiline protect neurons via increase expression of anti-apoptotic Bcl-2 and pro-survival neurotrophic factors in human neuroblastoma SH-SY5Y and glioblastoma U118MG cell lines.
Taken together, our findings demonstrate that KPNB1 is required for proteostasis maintenance and its inhibition induces apoptosis in glioblastoma cells through UPR-mediated deregulation of Bcl-2 family members.
We previously developed cell-penetrating VDAC1-derived peptides that interact with hexokinase (HK), Bcl-2, and Bcl-xL to prevent the anti-apoptotic activities of these proteins and induce cancer cell death, with a focus on leukemia and glioblastoma.
Our findings uncover a novel mechanism through which mitochondrial PKM2 phosphorylates Bcl2 and inhibits apoptosis directly, highlight the essential role of PKM2 in ROS adaptation of cancer cells, and implicate HSP90-PKM2-Bcl2 axis as a potential target for therapeutic intervention in glioblastoma.
Type B and A monoamine oxidase and their inhibitors regulate the gene expression of Bcl-2 and neurotrophic factors in human glioblastoma U118MG cells: different signal pathways for neuroprotection by selegiline and rasagiline.
Our results revealed that the Au PENPs were capable of delivering Bcl-2 siRNA to glioblastoma cells with an excellent transfection efficiency, leading to specific gene silencing in the target cells (22% and 25.5% Bcl-2 protein expression in vitro and in vivo, respectively) thanks to the RGD peptide-mediated targeting pathway.
TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2.
The antiapoptotic Bcl-2 family protein Mcl-1 is overexpressed in glioblastoma and represents an important resistance factor to the BH-3 mimetic ABT263.
In conclusion, these results suggested that GMFβ-dependent inactivation of the ERK1/2-Bcl-2/survivin pathway mediated the antiproliferative effect of β-elemene on glioblastoma.