Differentially expressed genes in ethanol extract of vanilla planifolia stem-induced cell death in glioblastoma cells

Abstract

Abstract Purpose Glioblastoma multiforme (GBM) is a highly malignant brain tumor with poor prognosis after conventional treatment. Therefore, novel therapeutic targets and potential treatment strategies have gained increased attention. Vanilla planifolia is an original source for vanilla flavoring due to its high vanillin content. Several studies have proven the antitumor activity of vanillin in colon cancer. Methods In this study, three GBM cell lines, patient-derived temozolomide (TMZ)-resistant GBM P#5 TMZ-R cells, T98G cells, and U-87 MG cells, were used to evaluate the antitumor activity of extracts from vanilla planifolia. Results Our data showed that ethanol extract of vanilla planifolia stem (VAS) at 200 ng/µl significantly reduced cell viability and colony formation of GBM cells. Moreover, VAS induced MAP1LC3 cleavage, a marker of autophagy. Further RNA-seq analysis and MA plot showed 1972 upregulated differentially expressed genes (DEGs) and 2276 downregulated DEGs in 200 ng/µl VAS-treated P#5 TMZ-R cells compared to the control. Protein-protein interaction between fold change of DEGs less than − 3 and over 5 were further analyzed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments showed that the mRNA expression of DHRS9, HOPX, AQP5, PCP4, RGS8, GNAT2, RLBP1, FA2H, TNMD, SKAP1, MATN1, IGFBP1, ELFN2, and C2CD4C was significantly downregulated. Moreover, the expression of IL36RN, CCL20, CCL5, CXCL10, HMOX1, MX2, RSAD2, IFI44L, and EGR1 was significantly upregulated. Conclusion These findings demonstrated that VAS reduced cell viability and colony formation, induced autophagy, and pinpointed some hub DEGs as potential therapeutic targets for GBM treatment.