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Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells.

ABSTRACT: Glioblastoma is an actively growing and aggressive brain tumor with a high propensity of recurrence. Although the surgical removal of tumor mass is the primary therapeutic option against glioblastoma, supportive pharmacotherapy is highly essential due to incredibly infiltrative characteristic of glioblastoma. Temozolomide, an FDA-approved alkylating agent, has been used as a first-line standard pharmacological approach, but several evident limitations were repeatedly reported. Despite additional therapeutic options suggested, there are no medications that successfully prevent a recurrence of glioblastoma and increase the five-year survival rate. In this study, we tested the possibility that finasteride has the potential to be developed as an anti-glioblastoma drug. Finasteride, an FDA-approved medication for the treatment of benign prostate hyperplasia and androgenic alopecia, is already known to pass through the blood-brain barrier and possess antiproliferative activity of prostate epithelial cells. We showed that finasteride inhibited the maintenance of glioma stem-like cells and repressed the proliferation of glioblastoma. Mechanistically, finasteride lowered intracellular ROS level by upregulating antioxidant genes, which contributed to inefficient β-catenin accumulation. Downregulated β-catenin resulted in the reduction in stemness and cell growth in glioblastoma.

SUBMITTER: Kim HJ

PROVIDER: S-EPMC8469955 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Asparagopsis taxiformis (Rhodophyta) is a species of red algae belonging to the family Bonnemaisoniaceae. The objective of the present study was to evaluate antioxidant and antiproliferative activity of four fractions (petroleum ether, chloroform, ethyl acetate, and methanol) of A. taxiformis.The red seaweed, A. taxiformis was collected from Mandapam Coastal Region, Gulf of Mannar, Tamil Nadu. Epiphytes present in algal extracts were cleaned and washed with seawater and fresh water. In vitro antioxidant activity was determined by hydrogen peroxide scavenging, ferric reducing antioxidant power, superoxide radical, metal-chelating activity, and phosphomolybdenum reduction assay. Further, the cytotoxic activity was evaluated using brine shrimp lethality assay. This method is rapid, reliable, inexpensive, and convenient as compared to other cytotoxicity assays. Gallic acid, ethylenediaminetetraacetic acid, ascorbic acid, and quercetin were used as reference antioxidant compounds.Reducing power of chloroform extract increased with increasing concentration of the extract. The radical scavenging activity of extracts was in the following order: ascorbic acid > methanol > chloroform > petroleum ether > ethyl acetate. Highest metal-chelating activity was observed in petroleum ether fractions (63%). Reduction of Mo (VI) to Mo (V) increased in methanol extract (27%) at 100 μg/ml. Moreover, all fractions had an inhibitory effect on the formation of hydroxyl radicals. Results showed that ethyl acetate, methanol, and petroleum ether fractions exhibited potent cytotoxic activity with median lethal concentration values of 84.33, 104.4, and 104.4 μg/ml, respectively.Thus, the results showed that red algae possess strong antioxidant and cytotoxic activity that suggests their possible use in the development of pharmaceutical drugs.Various fractions of red algae Asparagopsis taxiformis was evaluated for in vitro antioxidant and antiproliferative studies. All results indicate potential use of red algae for drug development. Abbreviations Used: Mo: Molybdenum, AlCl3.H2O: Aluminum chloride, NaNO2: Sodium nitrite, NaOH: Sodium hydroxide, H2O2: Hydrogen peroxide, NADH: Nicotinamide adenine dinucleotide, NBT: Nitroblue tetrazolium chloride, PMS: Phenyl methanesulfonate, FeCl2: Ferrous chloride.

Project description:Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. The poor prognosis and short median overall survival of patients with GBM is associated with resistance to therapy after surgical and adjuvant treatment. The expression of various acetylcholine receptors (AChR) in GBM has been widely reported. The present study aimed to investigate the expression of cholinergic system-related genes in primary GBM and to explore the antiproliferative effect of 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21) in GBM cell lines. Therefore, the expression of 28 genes associated with the cholinergic system was detected using a customized RT2 Profiler PCR Array in 44 GBM and 5 healthy control brain tissue samples. In addition, the activity of GTS-21, an alpha 7 subunit nicotinic AChR (α7 nAChR) agonist, and that of α-bungarotoxin (α-BTX), an α7 nAChR antagonist, was determined in primary and established GBM cells. Therefore, the A172, U87 and G28 cell lines and primary GBM cells were treated with GTS-21, ACh or nicotine. Cell viability was evaluated using MTT assay at 24, 48 and 72 h following cell treatment with the corresponding compounds. The results revealed that the expression of cholinergic system-related components was notably downregulated, except that of cholinergic receptor nicotinic alpha 7 subunit (CHRNA7), in primary GBM and U87 cells. However, the dominant-negative duplicate form of CHRNA7 was also downregulated. Furthermore, A172 and G28 cells exhibited a heterogeneous gene expression pattern. Additionally, GTS-21 inhibited the proliferation of GBM cells in a dose- and time-dependent manner. Interestingly, treatment with α-BTX restored the proliferation of U87 cells, but not that of A172 and G28 cells. Collectively, the findings of the present study suggested that GTS-21 may inhibit the proliferation of GBM cells and may therefore serve as a novel therapeutic approach to the treatment of GBM, which warrants further investigation.

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Antioxidant and Antiproliferative Activity of Finasteride against Glioblastoma Cells.

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