Biological Effects of Gyrophoric Acid and Other Lichen Derived Metabolites, on Cell Proliferation, Apoptosis and Cell Signaling pathways

Background and Aims: Hepatitis C virus (HCV) infection is an important risk factor for the development of liver cancer. The HCV NS3 protein plays a key role in the virus life cycle and can affect normal cellular activities, such as cell proliferation, cell death, and cell signaling pathways. Moreover, it may influence malignancy development. Two cellular genes, heat shock protein 70 (HSP70) and Glypican3 (GPC3), that are assessed in this study, play important roles in the regulation of the cell signaling pathways, including cell proliferation. This study aimed to evaluate the effects of HCV NS3 protein on the expressions of these two genes in the Balb/C mouse model. Materials and Methods: This study was performed on three groups of male mice of Balb/C (n=8). The first group received NS3 plasmid, the second group received hepatitis B virus HBx plasmid, and the negative control group received distilled water. Two injections were administered via the tail vein, and after the last injection, RNA was extracted from the liver tissue. Next, the cDNA synthesis and real-time polymerase chain reaction for relevant genes were performed. Results: Findings revealed that the relative expression of the selected genes in the NS3 group was significant in comparison with the negative control group (P=0.0229 for GPC3 and 0.0020 for HSP70). However, there was no significant difference between the NS3 group and the HBx group (P=0.4516 for GPC3 and 0.6740 for HSP70). Conclusion: Results showed that NS3 protein may affect the increasing expression of the mentioned genes. Nevertheless, for more precise understanding, much more studies should be performed, such as evaluation of the effect of NS3 on other involved proteins in cell signaling pathways, studying other domains of NS3, performance of pathological and histological tests, usage of various experimental methods, assessment of the role of NS4A as a cofactor for NS3, and usage of vectors with more stability.

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Therapeutic Potential of Polyphenols and their Nanoformulations in the Treatment of Colorectal Cancer

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666201231144007 ◽

2020 ◽

Vol 21 ◽

Author(s):

Shaheer H. Khan ◽

Fahad A. Alhumaydhi ◽

Masood A. Khan ◽

Hina Younus

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cell Signaling ◽

Signaling Pathways ◽

Cancer Cell ◽

Therapeutic Potential ◽

Aqueous Solubility ◽

Therapeutic Benefits ◽

Test Models ◽

Cell Signaling Pathways

Background: Colorectal cancer (CRC) ranks third among all cancer-related deaths around the globe. Chemotherapy may prolong the survival of CRC patients to some extent, but its clinical use is associated with grave side effects on overall health. Contrary to chemotherapy, the use of plant-derived therapeutic molecules offered advantages because of their reduced toxicity. Polyphenol is group of phytochemicals that impart many therapeutic benefits in the treatment of diabetes, cardiovascular disease and cancer. Various signaling pathways, including Wnt/β-catenin, MAPK/PI3K and TGF-β/Smad play very important roles in the development and progression of CRC. Polyphenols inhibit CRC progressions by modulating these signaling pathways e. g. curcumin and resveratrol impede cancer cell proliferation by inhibiting Wnt signaling. Because of their lower aqueous solubility, the therapeutic efficacy of polyphenols is not fully exploited. In order to increase their bioavailability and efficacy, the nanoformulations of polyphenols have been formulated and investigated against various CRC test models. The main objective of this review is to explore the potential roles of polyphenols and their nanoformulations in the treatment of colorectal cancer. Methods: We used PubMed, Web of Science, ScienceDirect, Google scholar and Scopus electronic databases by searching the keywords: Nanoparticles, Polyphenols, Colorectal cancer, Cell signaling pathways. Mostly, the articles were retrieved directly from the journals licensed to the library of Qassim University, Saudi Arabia. Results: Literature analysis has shown that the polyphenols contains several important bioactive compounds, which showed potential effectiveness against CRC. Incorporating polyphenols into nanoparticles further enhanced their bioavailability and efficacy. The findings from various studies demonstrated that polyphenol-nanoformulations accelerated the apoptosis in CRC cells by upregulating the levels of caspases and Bax, whereas inhibiting the CRC cell proliferation by dowregulating the expression of Bcl-2 and ERK1/2. Conclusions: This review provides a valuable resource on the important anti-CRC role of polyphenols and their nanoformulations. This review will expand our knowledge about the anti-CRC roles of polyphenols and their mechanisms of action through the multiple cell signaling pathways.

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