Propolis-loaded nanostructured lipid carriers halt breast cancer progression through miRNA-223 related pathways: an in-vitro/in-vivo experiment.

The most frequent malignant tumor in women is breast cancer, and its incidence has been rising every year. Propolis has been used for its antibacterial, antifungal, and anti-inflammatory properties. The present study aimed to examine the effect of the Egyptian Propolis Extract (ProE) and its improved targeting using nanostructured lipid carriers (ProE-NLC) in Ehrlich Ascites Carcinoma (EAC) bearing mice, the common animal model for mammary tumors. EAC mice were treated either with 5-fluorouracil (5-FU), ProE, ProE-NLC, or a combination of ProE-NLC and 5-FU. Their effect on different inflammatory, angiogenic, proliferation and apoptotic markers, as well as miR-223, was examined. ProE and ProE-NLC have shown potential anti-breast cancer activity through multiple interrelated mechanisms including, the elevation of antioxidant levels, suppression of angiogenesis, inflammatory and mTOR pathways, and induction of the apoptotic pathway. All of which is a function of increased miRNA-223 expression. The efficiency of propolis was enhanced when loaded in nanostructured lipid carriers, increasing the effectiveness of the chemotherapeutic agent 5-FU. In conclusion, this study is the first to develop propolis-loaded NLC for breast cancer targeting and to recommend propolis as an antitumor agent against breast cancer or as an adjuvant treatment with chemotherapeutic agents to enhance their antitumor activity and decrease their side effects. Tumor targeting by ProE-NLC should be considered as a future therapeutic perspective in breast cancer.

The diabetogenic effects of chronic supplementation of vitamin C or E in rats: Interplay between liver and adipose tissues transcriptional machinery of lipid metabolism.

AIM: The chronic administration of vitamin C and E can differentially disrupt hepatic insulin molecular pathway in rats. Hence, this study evaluated their effects on lipogenesis in the liver and adipose tissue and investigated the possible involvement of microRNA (miR)-22/29a/27a in the induced impaired glucose tolerance. MAIN METHODS: Wistar rats were orally supplemented with vitamin C (100, 200, and 500 mg/kg) or vitamin E (50, 100, and 200 mg/kg) for eight months. KEY FINDINGS: Vitamin C or E at the highest doses significantly altered liver weight and index, serum and hepatic lipids, adiponectin, and liver enzymes; besides their reported unfavorable effect on glucose homeostasis. Vitamin C and E negatively affected peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), sterol regulatory element-binding protein (SREBP)-1c/-2, miR-22/29a/27a expression, and adipose perilipin 1 to different extents, effects that were supported by the histopathological examination. SIGNIFICANCE: The current study provides a deeper insight into the findings of our previous study and highlights the detrimental effects of chronic vitamins supplementation on lipid metabolism. Overall, these findings emphasize the damage caused by the mindless use of supplements and reinforce the role of strict medical monitoring, particularly during the new COVID-19 era during which numerous commercial supplements are claiming to improve immunity.