Opuntiol Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells by Upregulating Active Caspase 3 Expression

Abstract

Background: Glioblastoma Multiforme (GBM) is a deadly tumor with poor prognosis. Resistance to apoptosis considered as an important factor in treatment failure. Therefore, identification of new compounds that facilitates apoptosis is crucial. Natural Anti-inflammatory compounds have emerged as potential anti-cancer agents and should be explored for their apoptotic activity against GBM. Therefore, the present study aims to evaluate growth inhibitory and apoptotic activity of a natural anti-inflammatory compound "Opuntiol" against GBM cell line U87. Methods: MTT assay was performed to determine the effect of Temozolomide and Opuntiol on growth inhibition of U87 cell. While, TUNEL assay was used to assess their apoptotic activity. To further assess apoptosis, nuclear condensation and nuclear area factor (NAF) was evaluated through DAPI staining. Whereas, active caspase-3 protein expression determined using immunocytochemistry. Results: Significant growth inhibition was observed in U87 cells treated with Temozolomide (IC50 380 µM) and Opuntiol (IC 50 357 µM). Temozolomide (p<0.001) and Opuntiol (p<0.001) significantly improved rate of apoptosis when compared to control group. A significant decrease in NAF was also observed in Temozolomide (p < 0.05) and Opuntiol (p < 0.05) treated cells. There was a significant increase in active caspase-3 expression when observed in Temozolomide (p<0.001) and Opuntiol (p<0.05) treated groups as compared to control. Conclusion: In conclusion our findings suggests, Opuntiol repress cell viability and possess strong apoptotic activity against GBM cell line U-87. However, further mechanistic studies will be required to confirm whether it can be develop as a potential drug against GBM.

Modulation of Apoptotic and Akt/PI3K/mTOR pathways to target Glioblastoma Cells using synthetic compound PGEA-AN

“…The cells were kept in incubator with humidified atmosphere at 37 0 C and 5% of carbon dioxide (CO 2 ). 17 The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyse the effect of test compounds on percentage inhibition of growth in the cells. Briefly, mono-layer of the cells in the flask was trypsinised using trypsin and ≈3000 cells/100μL of complete media was dispensed in 96-well plates.…”

“…The percentage of growth inhibition was determined by the formula: % growth inhibition of cells = 100-[(At -Ab)/ (Ac -Ab)] *100. 17 The half-maximal inhibitory concentration (IC50) was computed by the equation:…”

“…in which X 1 and X 2 denoted maximum and minimum doses to be utilised, and Y 1 and Y 2 denoted the mean percentage of viable cells at the maximum and minimum used doses. 17 The cells were treated with 10μM, 20μM and 30μM doses of PGEA-AN, and with 30μM, 40μM, 50μM, 100μM, 200μM of TMZ.…”

Repurposing synthetic and natural derivatives induces apoptosis in an orthotopic glioma‐induced xenograft model by modulating WNT/β‐catenin signaling

“…While the search for alternate therapeutic strategies to alleviate glioma pathogenesis is underway, previous studies had suggested that the overall prognosis in glioma patients can be improved by repurposing lead compounds of synthetic and natural origin, which, in turn, would improve the therapeutic efficacy of TMZ [5][6][7]. These therapeutic regimes, as adjuvants to the standard drug, can hamper glioma progression via modulation of signaling pathways with tolerable side effects [8][9][10][11].…”

Dynamics of repurposing synthetic and natural compounds against WNT/β-Catenin signaling in glioma- Anin vivoapproach

“…While the search for alternate therapeutic strategies to alleviate glioma pathogenesis is underway, previous studies had suggested that the overall prognosis in glioma patients can be improved by repurposing lead compounds of synthetic and natural origin, which in turn, would improve the therapeutic efficacy of TMZ (Xiao et al 2016; Ashfaque et al 2021; Precilla et al 2022). These therapeutic regimes, as adjuvants to the standard drug, can hamper glioma progression via modulation of signalling pathways with tolerable side effects (Kim et al 2010; Lu et al 2012; Wang et al 2016; Sargazi et al 2021).…”