Chemopreventive effect of spirulina microalgae on an animal model of glioblastoma via down-regulation of PI3K/AKT/mTOR and up-regulation of miR-34a/miR-125B expression.

Recent studies suggest that Spirulina may have great therapeutic benefits due to its antioxidant and anti-inflammatory properties. The primary objective of this study was to evaluate the chemopreventive properties of the Spirulina microalgae (Spi) on the regression and survival of tumor, histopathological features of glioblastoma, and detection of the molecular mechanism of Spi. Tumor viability versus Spi was determined using the MTT assay. In vivo antitumor activity of Spi was studied using the glioblastoma model. After tumor induction, the animals were euthanized, and their brains were removed. Histological evaluation was performed for tumor size and manifestation. The mechanisms of the anticancer effects of Spi were investigated by evaluating the microRNAs and their targets. The results demonstrated that Spi inhibited C6 and U87 cell proliferation and induced cell death. Histopathologic results showed that the administration of Spi could delay the development of tumors and prolonged the survival of tumor-bearing animals. Furthermore, Spi significantly upregulated miR-34a and miR-125b that have a key role in the progression of PI3K/AKT/mTOR pathway. This is the first in vivo report on the chemo-preventive effect of Spi against glioblastoma, suggesting its potential use in the chemoprevention of this cancer and the antiglioma molecular mechanism of Spi.

Evaluation of new bone formation in critical-sized rat calvarial defect using 3D printed polycaprolactone/tragacanth gum-bioactive glass composite scaffolds.

Critical-sized bone defects are a major challenge in reconstructive bone surgery and usually fail to be treated due to limited remaining bone quality and extensive healing time. The combination of 3D-printed scaffolds and bioactive materials is a promising approach for bone tissue regeneration. In this study, 3D-printed alkaline-treated polycaprolactone scaffolds (M-PCL) were fabricated and integrated with tragacanth gum- 45S5 bioactive glass (TG-BG) to treat critical-sized calvarial bone defects in female adult Wistar rats. After a healing period of four and eight weeks, the new bone of blank, M-PCL, and M-PCL/TG-BG groups were harvested and assessed. Micro-computed tomography, histological, biochemical, and biomechanical analyses, gene expression, and bone matrix formation were used to assess bone regeneration. The micro-computed tomography results showed that the M-PCL/TG-BG scaffolds not only induced bone tissue formation within the bone defect but also increased BMD and BV/TV compared to blank and M-PCL groups. According to the histological analysis, there was no evidence of bony union in the calvarial defect regions of blank groups, while in M-PCL/TG-BG groups bony integration and repair were observed. The M-PCL/TG-BG scaffolds promoted the Runx2 and collagen type I expression as compared with blank and M-PCL groups. Besides, the bone regeneration in M-PCL/TG-BG groups correlated with TG-BG incorporation. Moreover, the use of M-PCL/TG-BG scaffolds promoted the biomechanical properties in the bone remodeling process. These data demonstrated that the M-PCL/TG-BG scaffolds serve as a highly promising platform for the development of bone grafts, supporting bone regeneration with bone matrix formation, and osteogenic features. Our results exhibited that the 3D-printed M-PCL/TG-BG scaffolds are a promising strategy for successful bone regeneration.

Rutin: A Flavonoid as an Effective Sensitizer for Anticancer Therapy; Insights into Multifaceted Mechanisms and Applicability for Combination Therapy.

Rutin is a unique antioxidant flavonoid that is mainly found in fruit, vegetables, cereals, and many other plant-based human diets. This review aims to highlight the in vitro anticancer properties of rutin including combination therapeutic strategies. Literature resources were gathered through PubMed, Scopus, Web of Science, and Google Scholar databases that cover the period of 1995-2021. Rutin is demonstrated to inhibit the proliferation of breast, colon, lung, and prostate cancers and other tumors. Furthermore, rutin alone or in combination with other therapeutic agents has been shown to regulate several signalling pathways involving the Ras/Raf and PI3K/Akt, MAPK, and TGF-ß2/Smad2/3Akt/PTEN, etc., which are related to the processes of carcinogenesis and induction of apoptosis. The combination of rutin with other chemotherapy drugs may benefit on prevention of tumor cells by decreasing drug resistance and chemotherapy side effects. Moreover, rutin induces apoptosis synergistically with the therapeutic agent. More in vivo and clinical data are however needed to evaluate the true potential of rutin as an anticancer agent as an adjuvant. The present review highlights the effects of rutin which can be a promising candidate in combination with other antitumor drugs or alone for cancer treatment in vitro. Also, rutin can lead to decrease in drug resistance and chemotherapeutic side effects.

Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression.

Purpose: Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside from quercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects of rutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line (PC3) was investigated herein. Methods: Different concentrations of combined 5-FU and rutin were applied to PC3 cells compared to separate treatment for 48 hours. Cell viability, as well p53 gene expression respectively were assessed by MTT assay and real-time quantitative polymerase chain reaction (qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blot and flow cytometry procedures, respectively. Clonogenic assay was used to colony counts assessment. Results: 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and 5-FU respectively were 900 µM and 3Mm, while combination index (CI) of combined 5-FU /rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutin enhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2 signaling protein were decreased by 5-FU/rutin combination. Conclusion: Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis, p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separate application. 5-FU/rutin combination does seem an interesting therapeutic pathway to be further investigated.