Luteolin (LUT) is a natural flavonoid with low oral bioavailability with restricted clinical applications due to its low solubility. LUT shows significant anti-tumor activity in many cancer cells, including hepatocellular carcinoma (HCC). The most recent trend in pharmaceutical innovations is the application of phospholipid vesicles to improve the solubility of such hydrophobic drugs. Ethosomes are one of the most powerful phospholipid vesicles used to achieve that that target. In this study, LUT-loaded ethosomal nanoparticles (LUT-ENPs) were prepared by the cold method. Full factorial design and response surface methodology were used to analyze and optimize the selected formulation variables. Drug entrapment efficiency, vesicle size, zeta potential, Fourier transform infra-red spectroscopy, scanning electron microscopy, and cumulative percent drug released was estimated. The selected LUT-ENPs were subjected to further investigations as estimation of hepatic gene expression levels of GPC3, liver biomarkers, and oxidative stress biomarkers. The prepared LUT-ENPs were semi-spherical in shape with high entrapment efficiency. The prepared LUT-ENPs have a small particle size with high zeta potential values. The in vitro liver biomarkers assay revealed a significant decrease in the hepatic tissue nitric oxide (NO), malondialdehyde (MDA) content, and the expression of the GPC3 gene. Results showed a high increase in the hepatic tissue levels of glutathione (GSH) and superoxide dismutase (SOD). Histopathological examination showed a small number of hepatic adenomas and a significant decrease of neoplastic hepatic lesions after treatment with LUT-ENPs. Our results firmly suggest the distinctive anti-proliferative activity of LUT-ENPs as an oral drug delivery system for the treatment of HCC.
Thyroid cancer is among the most prevalent cancers with different types and stages. New markers are required for the prognosis and diagnosis of the disease. The present study aimed to detect the role of new markers, including galectin-3 (Gal-3) and thyroglobulin (TG), in the prognosis and staging of thyroid cancer. The study also investigated the potential apoptotic and inflammatory mechanisms involved in thyroid cancer through the determination of B-cell lymphoma 2 (Bcl-2), interleukin-8 (IL-8) and tumor necrosis factor α (TNFα) during the different stages of the cancer using a series of molecular methods. Histopathological and immunohistochemical examinations were also performed. A total of 300 subjects were classified into: 100 normal healthy subjects matched in age and sex, 100 patients with thyroid carcinoma stage I (T1N0M0) and 100 patients with thyroid carcinoma stage 2 (T2N1M1). Interestingly, the present study revealed a significant increase in the levels of TG and Gal-3 in thyroid cancer patients compared to the control group. Furthermore, the levels of Bcl-2, IL-8 and TNF-α significantly increased in the patient serum. The histopathological examination and immunohistochemical observations confirmed the molecular and hematological findings. Collectively, the present study concluded that serum TG and Gal-3 could be useful markers in the prognosis and staging of patients with thyroid cancer. Furthermore, the determination of Bax, Bcl-2, IL-8 and TNF-α levels constitute a major important marker for investigation of the mechanisms of apoptosis and inflammation in thyroid cancer. To our knowledge, this is the first study that used both galectin-3 and TG as tumor markers in the prognosis and differentiation between the different stages of cancer.
Plants from the genus Astragalus are gaining attention for their pharmacological importance. However, the information available regarding the HPLC–MS/MS chemical profile of A. fruticosus is inadequate. In this study, we performed HPLC–MS/MS analysis using electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). We tentatively identified 11 compounds in the A. fruticosus methanolic extract, including five flavonoidal and six saponin glycosides. The extract showed moderate antioxidant activity with 21.05% reduction in DPPH UV absorption. The preliminary cytotoxic screening against seven human cancer cell lines using 100 μg/mL extract showed prominent cytotoxic potential against colorectal cancer HCT–116 with 3.368% cell viability. It also showed moderate cytotoxic potential against prostate (DU–145), ovarian (SKOV–3) and lung (A–549) cancer cell lines with cell viability of 14.25%, 16.02% and 27.24%, respectively. The IC50 of the total extract against HCT–116 and DU–145 cell lines were 7.81 μg/mL and 40.79 μg/mL, respectively. The observed cytotoxicity of the total methanolic extract from the leaves against colorectal cancer might facilitate future investigations on cytotoxic agent(s) for disease management.
This study sheds the light on the potential of licorice (Glycyrrhiza glabra) root aqueous extract as a cornerstone for mitigating and detoxifying the residues of the widely used agricultural Glyphosate-based pesticides (GBPs). This study examined the GBPs toxic effects on kidney, liver, thyroid functions, and apoptosis using 50 adult male albino rats. All rats were divided into 5 groups, with 10 each. Control: served as untreated rats. GBP: rats were treated with 1 mL glyphosate solution 24 % orally for three weeks. The glyphosate-treated rats were gavaged with licorice root aqueous extractsolution (100, 200, and 300 mg/mLdistilled water, respectively) daily for three weeks. Licorice root aqueous extract solution (300 mg/mL distilled water) yielded notable reductions in liver, kidney enzymes, albumin, and AFP levels within the serum. Immunological tests, including immunohistochemical evaluations of caspase-3 and TNF-α expressions revealed a dose-dependent attenuation of apoptosis and inflammation with licorice intervention. This will provide a valuable perspective for agricultural practices future and paving the way for a more sustainable approach for using GBPs in animal agriculture industries.
There is a growing interest in discovering natural sources of anti-cancer drugs. Sesamol (SES) is a phenolic compound with antitumor effects. The present study aimed to investigate the anticancer properties of SES and its nano-suspensions (SES-NS) combined with Epirubicin (EPI) in breast cancer (BC) using mice bearing a solid Ehrlich tumor. The study involved 35 female albino mice and investigated the effects of SES and EPI on tumor growth, proliferation, apoptosis, autophagy, angiogenesis, and oxidative stress. Methods including ELISA, qRT-PCR, and immunohistochemistry were utilized. The findings revealed reductions in tumor growth and proliferation using SES either alone or combined and evidenced by decreased AKT (AKT Serine/Threonine kinase1) levels, angiogenesis indicated by lower levels of VEGFR (vascular endothelial growth factor), and apoptosis demonstrated by elevated caspase3 and BAX levels. Furthermore, autophagy increased and was indicated by increased levels of beclin1 and lc3, along with decreased oxidative stress as evidenced by elevated TAC (total antioxidant capacity) and reduced MDA (malondialdehyde) levels. Interestingly, SES-NS demonstrated more significant effects at lower doses. In summary, this study underscores the potential of SES as a promising agent for BC treatment. Moreover, SES-NS potentiated the beneficial effects of EPI while mitigating its adverse effects.