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Antiproliferative and apoptotic effects of telmisartan in human glioma cells.

ABSTRACT: Glioblastoma is the most common primary central nervous system tumor in adults. Angiotensin II receptor blockers (ARBs) are broadly applied to treat hypertension. Moreover, research has revealed that ARBs have the capacity to suppress the growth of several cancer types. In this study, we assessed the effects of three ARBs with the ability to cross the blood brain barrier (telmisartan, valsartan and fimasartan) on cell proliferation in three glioblastoma multiforme (GBM) cell lines. Telmisartan markedly suppressed the proliferation, migration, and invasion of these three GBM cell lines. Microarray data analysis revealed that telmisartan regulates DNA replication, mismatch repair, and the cell cycle pathway in GBM cells. Furthermore, telmisartan induced G0/G1 phase arrest and apoptosis. The bioinformatic analysis and western blotting results provide evidence that SOX9 is a downstream target of telmisartan. Telmisartan also suppressed tumor growth in vivo in an orthotopic transplant mouse model. Therefore, telmisartan is a potential treatment for human GBM.

SUBMITTER: Chang YL

PROVIDER: S-EPMC10251602 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Antiproliferative and apoptotic effects of telmisartan in human glioma cells.

Chang Yung-Lung YL Chou Chung-Hsing CH Li Yao-Feng YF Huang Li-Chun LC Kao Ying Y Hueng Dueng-Yuan DY Tsai Chia-Kuang CK

Cancer cell international 20230609 1

Glioblastoma is the most common primary central nervous system tumor in adults. Angiotensin II receptor blockers (ARBs) are broadly applied to treat hypertension. Moreover, research has revealed that ARBs have the capacity to suppress the growth of several cancer types. In this study, we assessed the effects of three ARBs with the ability to cross the blood brain barrier (telmisartan, valsartan and fimasartan) on cell proliferation in three glioblastoma multiforme (GBM) cell lines. Telmisartan m ...[more]

PMID: 37291545

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Project description:BACKGROUND:Nigella sativa (NS), a member of family Ranunculaceae is commonly known as black seed or kalonji. It has been well studied for its therapeutic role in various diseases, particularly cancer. Literature is full of bioactive compounds from NS seed. However, fewer studies have been reported on the pharmacological activity of proteins. The current study was designed to evaluate the anticancer property of NS seed proteins on the MCF-7 cell line. METHODS:NS seed extract was prepared in phosphate-buffered saline (PBS), and proteins were precipitated using 80% ammonium sulfate. The crude seed proteins were partially purified using gel filtration chromatography, and peaks were resolved by SDS-PAGE. MTT assay was used to screen the crude proteins and peaks for their cytotoxic effects on MCF-7 cell line. Active Peaks (P1 and P4) were further studied for their role in modulating the expression of genes associated with apoptosis by real-time reverse transcription PCR. For protein identification, proteins were digested, separated, and analyzed with LC-MS/MS. Data analysis was performed using online Mascot, ExPASy ProtParam, and UniProt Knowledgebase (UniProtKB) gene ontology (GO) bioinformatics tools. RESULTS:Gel filtration chromatography separated seed proteins into seven peaks, and SDS-PAGE profile revealed the presence of multiple protein bands. Among all test samples, P1 and P4 depicted potent dose-dependent inhibitory effect on MCF-7 cells exhibiting IC50 values of 14.25?±?0.84 and 8.05?±?0.22??g/ml, respectively. Gene expression analysis demonstrated apoptosis as a possible cell killing mechanism. A total of 11 and 24 proteins were identified in P1 and P4, respectively. The majority of the proteins identified are located in the cytosol, associate with biological metabolic processes, and their molecular functions are binding and catalysis. Hydropathicity values were mostly in the hydrophilic range. CONCLUSION:Our findings suggest NS seed proteins as a potential therapeutic agent for cancer. To our knowledge, it is the first study to report the anticancer property of NS seed proteins.

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Antiproliferative and apoptotic effects of telmisartan in human glioma cells.

Publications

Antiproliferative and apoptotic effects of telmisartan in human glioma cells.

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