Evaluation of the Combined Effect of Caffeine and 5-Fluorouracil on Colorectal Cancer Cell Lines.

BACKGROUND: Cancer is the second leading cause of death in the world. Colorectal cancer is the third leading cause of cancer death. Today, there are several options for treating colorectal cancer such as chemotherapy, surgery, radiotherapy, immunotherapy, and gene therapy. 5-Fluorouracil is known as a suitable candidate for the treatment of various cancers, especially colorectal cancer. However, the use of this drug is limited, so it is usually used in combination with other drugs and agents. Based on the evidence obtained, this study attempted to evaluate the combined effects of 5-fluorouracil and caffeine on colorectal cancer cells. METHODS: In this study, initially HCT116 and HEK293 cell lines were cultured as cancer and normal cells, respectively. These cell lines were then evaluated for cytotoxicity, induction of apoptosis, and rate of cell migration. All data were analyzed by statistical methods. RESULTS: The results indicated that a combination of caffeine and 5-FU augmented their cytotoxicity in HCT116 cells but reduced cytotoxicity in HEK293 cells. No reduction was observed in the migration of HCT116 cells that were treated with caffeine or a combination of caffeine and 5-FU. Also, it seems that caffeine reverses the apoptotic effect of 5-FU in HCT116 cells.

Highlighting functions of apoptosis and circular RNAs in colorectal cancer.

Colorectal cancer (CRC) is known as one of the global problems that endangers the lives of thousands of people every year. Various treatments have been used to deal with this disease, but in some cases, they are not effective. Circular RNAs, as a novel class of noncoding RNAs, have different expression levels and various functions in cancer cells, such as gene regulation through microRNA sponging. They play an important role in various cellular processes, including differentiation, proliferation, invasion, and apoptosis. Changes in the process of apoptosis are closely related to the progression or inhibition of various malignancies. Induction of apoptosis in cancer cells is a promising target for tumor therapy. In this study, circRNAs were investigated as being central to the induction or inhibition of apoptosis in CRC. It is hoped that through targeted changes in the function of these biomolecules, better outcomes will be achieved in cancer treatment. Perhaps better outcomes for cancer treatment can be achieved by using new methods and modifying the expression of these nucleic acids. However, using this method may come with challenges and limitations.

A review on nonviral, nonbacterial infectious agents toxicity involved in neurodegenerative diseases.

Neuronal death, decreased activity or dysfunction of neurotransmitters are some of the pathophysiological reasons for neurodegenerative diseases like Alzheimer's, Parkinson's and multiple sclerosis. Also, there is evidence for the role of infections and infectious agents in neurodegenerative diseases and the effect of some metabolites in microorganisms in the pathophysiology of these diseases. In this study, we intend to evaluate the existing studies on the role of infectious agents and their metabolites on the pathophysiology of neurodegenerative diseases. PubMed, Scopus, Google Scholar and Web of Science search engines were searched. Some infectious agents have been observed in neurodegenerative diseases. Also, isolations of some fungi and microalgae have an improving effect on Parkinson's and Alzheimer's.

Nanoparticles: The future of effective diagnosis and treatment of colorectal cancer?

Colorectal cancer (CRC) is one of the most challenging malignancies in terms of diagnosis and treatment. Conventional diagnostic methods are primarily based on colonoscopy and often lack accuracy, while standard treatment options typically include chemotherapy, which can be unsuccessful due to side effects and (development of) drug resistance. Although new diagnostic methods and timely screening have decreased the death rate from cancer in developed countries in recent years, there still is an urgent need for (novel) therapeutic strategies that render better disease management and clinical outcomes. Nanoparticles (NPs) have emerged as promising candidates for the improvement of diagnosis and treatment by promoting drug targeting, solubility and bioavailability. For example, NPs can reduce toxicity of drugs by increasing solubility and can be engineered to specifically target malignancies, thereby minimizing unwanted side effects. In this review, we evaluated the potential of implementing various NPs for the diagnosis and treatment of CRC.

Binding Sites of Anticancer Drugs on Human Serum Albumin (HSA): A Review.

BACKGROUND: To recognize the action of pharmacologically approved anticancer drugs in biological systems, information regarding its pharmacokinetics, such as its transport within the plasma and delivery to its target site, is essential. In this study, we have tried to collect and present complete information about how these drugs bind to human serum albumin (HSA) protein. HSA functions as the main transport protein for an enormous variety of ligands in circulation and plays a vital role in the efficacy, metabolism, distribution, and elimination of these agents. METHODS: Therefore, this study includes information about the quenching constant, the binding constant obtained from Stern-Volmer and Hill equations, and molecular docking. RESULTS: Molecular docking was carried out to detect the binding models of HSA-anticancer drugs and the binding site of the drugs in HSA, which further revealed the contribution of amino acid residues of HSA in the drug complex binding. CONCLUSION: This review study showed that site I of the protein located in domain II can be considered the most critical binding site for anticancer drugs.

Molecular landscape of c-Myc signaling in prostate cancer: A roadmap to clinical translation.

The c-Myc signaling is a new emerging target in cancer therapy. Activation of c-Myc signaling leads to cancer growth and invasion in vitro and in vivo. The stability of c-Myc can also mediate drug resistance and radioresistance in cancers. The apoptosis inhibition and enhancing cell cycle progression are mediated by c-Myc overexpression. On the other hand, prostate cancer (PC) is the most common cancer in men and causes high death. The present review focuses on c-Myc signaling in PC. The c-Myc overexpression is in favor of PC growth and migration. Upon c-Myc inhibition, apoptosis and cell cycle arrest (G0/G1 phase) occur in PC cells. The c-Myc induces glycolysis in enhancing PC growth. Besides, stability and overexpression of c-Myc can mediate resistance of PC cells to chemotherapy and radiotherapy. The inhibition of c-Myc by both anti-tumor agents and genetic tools suppress PC progression. The miRNAs, lncRNAs, circRNAs and other factors such as PI3K/Akt can act as upstream regulator of c-Myc signaling. The c-Myc can function as independent prognostic and diagnostic factor in PC patients. The c-Myc upregulation is associated with reduced overall survival, clinical stage, lymph node metastasis and undesirable prognosis of PC patients.

The Effect of NeuroAid (MLC901) on Cholestasis-Induced Spatial Memory Impairment with Respect to the Expression of BAX, BCL-2, BAD, PGC-1α and TFAM Genes in the Hippocampus of Male Wistar Rats.

Cholestasis is a bile flow reduction that is induced following Bile Duct Ligation (BDL). Cholestasis impairs memory and induces apoptosis. Apoptosis consists of two pathways: intrinsic and extrinsic. The intrinsic pathway is modulated by BCL-2 (B cell lymphoma-2) family proteins. BCL-2 (a pro-survival BCL-2 protein) has anti-apoptotic effect, while BAD (BCL-2-associated death) and BAX (BCL-2-associated X), the other members of BCL-2 family have pro-apoptotic effect. Furthermore, TFAM (mitochondrial transcriptional factor A) is involved in transcription and maintenance of mitochondrial DNA and PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) is a master regulator of mitochondrial biogenesis. On the other hand, NeuroAid is a Traditional Chinese Medicine with neuroprotective and anti-apoptosis effects. In this study, we evaluated the effect of cholestasis on spatial memory and expression of BCL-2, BAD, BAX, TFAM, and PGC-1α in the hippocampus of rats. Additionally, we assessed the effect of NeuroAid on cholestasis-induced cognitive and genetic alterations. Cholestasis was induced by BDL surgery and NeuroAid was injected intraperitoneal at the dose of 0.4 mg/kg. Furthermore, spatial memory was evaluated using Morris Water Maze (MWM) apparatus. The results showed cholestasis impaired spatial memory, increased the expression of BAD and BAX, decreased the expression of TFAM and PGC-1α, and did not alter the expression of BCL-2. Also, NeuroAid decreased the expression of BAD and BAX and increased the expression of TFAM, PGC-1α, and BCL-2. In conclusion, cholestasis impaired spatial memory and increased the expression of pro-apoptotic genes. Also, cholestasis decreased the expression of TFAM and PGC-1α. Interestingly, NeuroAid restored the effects of cholestasis.