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5-Hydroxy-3′,4′,6,7-tetramethoxyflavone (TMF) is a plant-origin flavone known for its anti-cancer properties. In the present study, the cytotoxic effect of TMF was evaluated in the U87MG and T98G glioblastoma (GBM) cell lines. The effect of TMF on cell viability was assessed with trypan blue exclusion assay and crystal violet staining. In addition, flow cytometry was performed to examine its effect on the different phases of the cell cycle, and in vitro scratch wound assay assessed the migratory capacity of the treated cells. Furthermore, the effect of in vitro radiotherapy was also evaluated with a combination of TMF and radiation. In both cell lines, TMF treatment resulted in G0/G1 cell cycle arrest, reduced cell viability, and reduced cell migratory capacity. In contrast, there was an antagonistic property of TMF treatment with radiotherapy. These results demonstrated the antineoplastic effect of TMF in GBM cells in vitro, but the antagonistic effect with radiotherapy indicated that TMF should be further evaluated for its possible antitumor role post-radiotherapy.

Background/Objectives: Glioblastoma (GBM) is the most aggressive type of brain tumor in adults. Currently, the only treatments available are surgery, radiotherapy, and chemotherapy based on temozolomide (TMZ); however, the prognosis is dismal. Several natural substances are under investigation for cancer treatment. 8α-O-(3,4-dihydroxy-2-methylenebutanoyloxy) dehydromelitensine (Isocnicin) is a natural compound derived from Centaurea species and was found to exhibit cytostatic/cytotoxic effect against different cell lines. In this study, we investigated the anti-glioma effects of isocnicin in U87 and T98 glioblastoma cell lines, as well as the effects of combined treatment with radiotherapy. Methods: Cell viability was evaluated with the trypan blue exclusion assay, cell cycle distribution was examined using flow cytometry, and the effects of the combination treatment were analyzed with CompuSyn software(1.0). Results: The result showed that isocnicin significantly reduced cell viability in U87 and T98 cell lines in a dose-dependent manner and IC50 values were calculated. Administration of isocnicin alone induced both S and G2/M cell cycle arrest in U87 and T98 cells in a dose-dependent manner. Moreover, when cells were treated with increasing concentrations of isocnicin, followed by 2 or 4 Gy of radiation, the percentage distribution of the cells in the G2/M phase was increased considerably in both U87 and T98 cell lines. Conclusions: Here, we show for the first time that co-treatment of isocnicin with radiation exerts a synergistic antiproliferative effect in glioblastoma cell lines. Natural compounds are promising for glioblastoma treatment. Further studies will be necessary to unravel isocnicin's mechanism of action and its synergistic effect with radiation on glioblastoma treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer has a major impact on societies across the world. In an attempt to find new treatment options for cancer, attention has shifted to natural compounds. Curcumin is a polyphenol isolated from the roots of turmeric that possesses many biological properties. It acts on the regulation of different aspects of tumor development and interconnects with major signaling pathways that are dysregulated in cancer, such as the phosphatidylinositol-3-kinase/protein kinase B pathway. In this review, the diverse effects of curcumin on the regulation of this pathway in different malignancies will be discussed. Cancer is a life-threatening disease and one of the leading causes of death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures have been investigated for their multimodal anti-cancer properties. Curcumin is a polyphenol isolated from the rhizomes of Curcuma longa and has been widely studied for its anti-inflammatory, anti-oxidant, and anti-cancer effects. Curcumin acts on the regulation of different aspects of cancer development, including initiation, metastasis, angiogenesis, and progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway is a key target in cancer therapy, since it is implicated in initiation, proliferation, and cancer cell survival. Curcumin has been found to inhibit the PI3K/Akt pathway in tumor cells, primarily via the regulation of different key mediators, including growth factors, protein kinases, and cytokines. This review presents the therapeutic potential of curcumin in different malignancies, such as glioblastoma, prostate and breast cancer, and head and neck cancers, through the targeting of the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

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