Telmisartan attenuates human glioblastoma cells proliferation and oncogenicity by inducing the lipid oxidation

Abstract

Background Glioblastoma (GBM) is one of the most common primary brain tumors, which accounts up to 80% of malignant brain tumors and the 5‐year relative survival rate is below 5%. Recent studies showed that the lipid metabolism played an essential role in GBM development. As a peroxisome proliferators‐activated receptors γ (PPAR‐γ) agonist, telmisartan improves the lipid metabolism and has been used to treat hypertension for long time. It has also been shown to have anticancer function, such as in lung cancer and melanoma. Methods Incucyte real‐time live cell imaging system was used to assess the effect of telmisartan on glioma cell lines U87 and U251 proliferation. Transwell assay and colony formation assay were conducted to detect the effect of telmisartan on oncogenicity of GBM cell lines. Western blot and immunofluorescence analysis were used to detect the effect of telmisartan on the expression of PPAR‐γ and hydroxyacyl‐coenzyme A dehydrogenase alpha subunit (HADHA). Results We demonstrate that telmisartan inhibits two glioma cell lines U87 and U251 proliferation in a time‐ and dose‐dependent manner, and arrests the cell cycle at S phase. We further show that telmisartan decreases the oncogenicity of GBM cell lines. Our data show that telmisartan treatment significantly increases the PPAR‐γ expression level, enhances the lipid oxidation, and upregulates the level of fatty acid oxidation key enzyme HADHA. Conclusions Telmisartan inhibits the proliferation and oncogenicity while it also increases the lipid oxidation of human GBM cells.

Telmisartan loaded lipid nanocarrier as a potential repurposing approach to treat glioma: characterization, apoptosis evaluation in U87MG cells, pharmacokinetic and molecular simulation study

“…Singh et al, 2024 in his recent study have demonstrated potential anticancer effect of TS loaded nanocarrier in breast cancer [12]. Another work by Wang et al, 2021 showed effectiveness of TS delivered through solid-lipid nanoparticles again brain cancer [13]. The current research investigation, however, will differ significantly from all previously reported works of this type.…”

Evidence of Omics, Immune Infiltration, and Pharmacogenomic for SENP1 in the Pan-Cancer Cohort

“…The studies indicated Telmisartan can be used to treat ESCA (Matsui et al, 2019), EAC (Fujihara et al, 2017), CHOL (Samukawa et al, 2017), and hematologic malignancies (Kozako et al, 2016). It has also been reported that Telmisartan can apply in the treatment of endometrial (Koyama et al, 2014), lung cancers (Rasheduzzaman et al, 2018), bladder and urological (Matsuyama et al, 2010), ovarian (Pu et al, 2016), colon (Lee et al, 2014), renal (de Araújo Júnior et al, 2015, prostate (Funao et al, 2008), gastric (Fujita et al, 2020), and breast (Kociecka et al, 2010) cancers, hepatocellular carcinoma (Oura et al, 2017), and GBM (Wang et al, 2021). Nilotinib can also be used to treat CHOL (Marin et al, 2018), DLBC (Robak and Robak, 2012;Cai et al, 2019), and THYM (Kelly, 2013;Simonelli et al, 2015).…”

MDACT: A New Principle of Adjunctive Cancer Treatment Using Combinations of Multiple Repurposed Drugs, with an Example Regimen

“…PPARγ is upregulated in mesenchymal glioblastoma stem cells, with agonism suppressing growth [329]. D. Telmisartan in NSCLC: Several studies show longer survival in NSCLC in patients receiving an ARB [330][331][332][333]. This effect, although slight, has been consistently found across studies.…”