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Objective: To determine the anticancer potential of the methanolic extract from Ephedra alata against breast cancer both in vitro and in vivo. Methods: The effects of the methanolic extract of Ephedra alata on the viability, migration as well as apoptosis of breast cancer 4T1 cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Transwell assay, and annexin V-FITC staining assay, respectively. Histological examination was also carried out. Moreover, a murine breast cancer model was established to evaluate the inhibitory effect of the extract. Biochemical parameters including hepatic and non-hepatic enzymes, malondialdehyde, and glutathione were investigated. Results: The methanolic extract of Ephedra alata showed a strong anti-proliferative and anti-migratory activity against 4T1 cells in a dose-dependent manner. It also induced apoptosis in 4T1 cells. In an in vivo mouse model, the extract markedly inhibited tumor growth, reduced malondialdehyde, and hepatic and non-hepatic enzymes as well as increased glutathione level. Conclusions: The methanolic extract of Ephedra alata inhibits breast cancer in vitro and in vivo, which may be a promising anticancer agent.

Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-smallcell lung cancer accounts for 85%–90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1. Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-smallcell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition. Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness. Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood–brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases “in one shot.” Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment. [ABSTRACT FROM AUTHOR]

Cancer is a class of diseases characterized by uncontrolled cell growth. One of the main aims of developing new therapies is to use natural resources to induce apoptosis. LC-ms/ms analysis of a methanolic extract of Ephedra alata (E.A.) allowed the identification of 20 secondary metabolites, including flavonoids, phenolic acids, and proanthocyanidins. Antiproliferative effect was assessed by crystal violet assay. Antimigration effect was tested by wound healing assay and apoptosis induction was determined by annexin binding assays, Hoechst staining, ROS production, and activation of apoptotic proteins. The results indicated that exposure of breast cancer cells to E.A. extract significantly reduced cell viability in a dose and time-dependent manner and inhibited the migration of 4T1 cells at a low dose. Moreover, treatment of cells with E.A. extract induced apoptosis, as it was detected by Annexin V/7 AAD, Hoechst staining, ROS production, and the activation of caspases. Abbreviation: BSA bovine serum albumin DMSO dimethyl sulfoxide EDTA ethylenediaminetetraacetic acid LC-ms/ms liquid chromatography-mass spectrometry NAC N-acetyl-l-cysteine PARP poly(ADP-ribose) polymerase PMSF phenylmethylsulfonyl fluoride RIPA radioimmunoprecipitation assay buffer ROS reactive oxygen species RPMI Roswell park memorial institute SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis. [ABSTRACT FROM AUTHOR]

Melanoma has become an important health problem and new treatment have become an imperative medical need. Therefore, the finding and identification of natural product with less toxic effects, capable of promoting melanoma cell death have become an important goal of research in oncotherapy. In this study, we want to investigate the anticancer activity of an enriched total oligomers flavonoids (TOF) extract of R. alaternus in melanoma cells. First, TOF was exhibited to be rich in flavones. We revealed that this extract reduced proliferation and increased of sub-G1 and S phase cells built-up in B16-F10 cells in a dose-related manner. Moreover, In Vivo, TOF reduced tumor volume and weight with percentages of inhibition of 92.4% and 92.9%, respectively. R. alaternus was also found to be effective in reducing the level of pro-inflammatory cytokine IL-6 during metastasis. Level of TH1 cytokine, such as IL-2, was significantly enhanced by TOF treatment. Indeed, the histological examination of the tumor revealed the absence of mitoses and the presence of numerous melanin pigmented macrophage cells in the R. alaternus extract-treated group that could be explained by the induction of macrophage activation and by the arrest of the cell cycle in the Sub-G1 and S phases. [ABSTRACT FROM AUTHOR]