Jentashapir Journal of Cellular and Molecular Biology
Volume:14 Issue: 3, Sep 2023

A highly conserved kinase cascade, including mammalian STE20-like protein kinases (MSTs), large tumor suppressors (LATSs), and downstream transcription coactivators containing YES-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are involved in the Hippo signaling pathway. As two critical transcriptional coactivators, TAZ and YAP are adversely regulated by the Hippo signaling pathway. They lead to the induction of organ regeneration and the expression of cell growth and division-promoting genes through binding to transcription factors, especially TEA domain transcription factors (TEADs). Previous studies highlight the role of the Hippo pathway in organ size control, homeostasis, cell proliferation, and tumor development. Research has shown this pathway's vital role in cancer stem cell biology, including self-renewal and drug resistance. Improper activation of YAP and TAZ through the Hippo pathway dysregulation or its increased expression can accelerate tumorigenesis. Thus, pharmacological inhibition of YAP and TAZ is suggested as a promising approach in the treatment of tumors with high YAP/TAZ activity.

Context: 

Cellular metabolism is a set of controlled biochemical reactions known as metabolic pathways that occur in living organisms in order to sustain life. Cells may use different metabolic pathways and alter metabolism to use more effective processes for survival depending on cellular conditions. Alterations in metabolic pathways can lead to the transformation of normal cells into cancerous cells, leading to cancer initiation and development.

 Proper cellular conditions in terms of pH and the availability of essential nutrients and oxygen are important for the healthy functioning of aerobically respiring human cells. If cells are exposed to stressors such as carcinogens that can induce mutations in the genes involved in metabolic pathways, anaerobic metabolism may be used by cells, turning them into cancerous cells. Cellular conditions that maintain aerobic cellular respiration and mitigate the effects of cellular stressors can improve cells’ resistance to neoplastic transformation.

 This paper explores the key metabolic pathways used by cancer cells as a function of their environmental conditions based on the Warburg effect. In addition, some analyses and studies were conducted on global and regional cancer incidence rates, taking into account changes in lifestyle and dietary patterns.
Results and

 Natural resistance to cancer may be improved when cells grow in healthy conditions at molecular levels, requiring a balanced alkalizing diet and healthy lifestyle, as well as reduced exposure to environmental carcinogens, which are key control factors. In particular, effective nutritional interventions can help normal cells resist metabolic changes underlying cancer development.

 Protein phosphatases (PP2Cs) are the main classes of protein phosphatases in plants, having pivotal functions in different plant stages and abiotic stresses. The PP2C genes are suggested to have critical roles in barley by exposure to heat and cold treatments.

 We surveyed HvPP2C genes from the barley genome in the present study. Phylogenetic analysis, functional annotation, synteny analysis, chromosomal distribution, prediction of cis-elements, and gene expression of HvPP2Cs under abiotic stresses were studied.

 In this study, HvPP2Cs of barley were surveyed using bioinformatics tools, and HvPP2C gene expression profiles under cold and heat stresses in 3 tissues (root, leaf, and stem) were analyzed.

 In this study, 61 HvPP2C genes were detected from barley, and a phylogenetic tree was divided into 13 subfamilies. The results of chromosomal distribution showed that the HvPP2C genes were located on 7 chromosomes. Real-time quantitative reverse transcription PCR (qRT-PCR) analysis of HvPP2Cs showed that they were largely expressed in different tissues (root, stem, and leaf) in the Azaran and Jolge barley cultivars. In Azaran, the HvPP2C gene expression increased in response to cold stress, whereas, in the Jolge cultivar, the HvPP2C gene expression increased in response to heat stress. The analysis of synteny revealed that HvPP2C24b with HvPP2C24a, HvPP2C24 with HvPP2C24a and HvPP2C24b; HvPP2C5 with HvPP2C5a, and HvPP2C41 with HvPP2C41a were paralogous.

 Results revealed a broad understanding of the HvPP2C gene family in barley, which can be valuable for the functional description of HvPP2Cs in plant response to abiotic stresses.

 The production of recombinant human growth hormone is usually problematic in Escherichia coli, and achieving higher functional protein yields is economically important.

 In this study, the chromosomal expression of recombinant human growth hormone (hGH) in the araBAD operon was investigated using Rosetta-gami and BL21 (DE3) competent cells under the regulation of arabinose and T7 promoters using arabinose inducer and IPTG, respectively. Subsequently, the expression of the plasmid-based protein was examined using pET28 (a) + plasmid in Rosetta-gami under the T7 promoter, and the results were compared.

 The lambda red technique was used to integrate the desired gene into the host genome. The Fh8 tag was used to increase the protein’s expression, solubility, and thermal resistance.

 The recombinant BL21 (DE3) under the T7 promoter and the recombinant Rosetta-gami containing pET28-Fh8-hGH plasmid showed significant expression among the chromosome-based and plasmid-based strains, respectively. Preliminary studies on the solubility and thermal resistance of the produced proteins indicated the efficacy of the Fh8 tag in increasing the expression, solubility, and thermal resistance of the product.

 One advantage of the genomic expression approach is the stability of the gene in the genome. Also, the lack of the need to use antibiotics in production systems can effectively reduce the production costs of this widely used hormone. In addition, the presence of the Fh8 tag can facilitate and accelerate its purification process by increasing the heat resistance thermostability of growth hormone.

 Thyroid cancer is the most common endocrine cancer, and women are almost three times more likely to develop it than men.

 The etiology of thyroid cancer at the genetic level remains elusive. However, a potential involvement of the RNA Transcription, Translation, and Transport Factor (RTRAF) gene in the pathogenesis of this malignancy has been postulated. This gene has been shown to govern the expression of proteins that exert regulatory effects on the transition from the G1 to S phase of the cell cycle.

 For this study, 22 papillary thyroid carcinoma (PTC) tissues and 22 healthy tissues were collected. Additionally, 10 benign goiter tissues and 10 healthy tissues were gathered. RNA molecules were fixed, and complementary DNA (cDNA) was produced. Specific primers were used to measure the RTRAF gene expression. Statistical analysis was conducted using REST 2009 software.

 Upon assessing the quality and quantity of RNA, it was ascertained that the extracted RNA molecules exhibited minimal damage and were found to be appropriately concentrated for cDNA production. The amplification of the RTRAF gene was carried out accurately, as evidenced by the melting curve. A noteworthy decline in the RTRAF gene expression was detected in the benign goiter tissue compared to the adjacent healthy tissue, with a relative expression of 0.154 and a statistical value of P = 0.002. Conversely, there was no significant difference in the RTRAF gene expression between PTC and the adjacent healthy tissue, with a P-value of 0.808.

 The reduced RTRAF gene expression in benign thyroid tumors may hinder cancer cell growth, as no difference was observed between malignant PTC tumor tissues and their healthy tissues.

Large intestine cancer, also known as colon cancer or rectal cancer, is a type of cancer that affects the colon or rectum. It is the third most common cause of cancer-related deaths worldwide, and in Iran, it ranks as the fourth most common cancer among men and the second most common cancer among women. Some of the common symptoms of this disease include intestinal rupture and obstruction, abdominal pain, nausea and vomiting, the presence of blood in the stool, and constant fatigue. Common methods of cancer treatment include surgery, radiation therapy, and chemotherapy. New methods of cancer treatment include gene therapy, hormone therapy, and nanotechnology. Nanoparticles (NPs), which contain particles in the size range of 1 to 100 nanometers, are used in nanotechnology. These NPs can originate from natural or human sources and have shown unprecedented growth in the field of research and applications of nanotechnology, especially in the treatment of cancer.

The objective of this study was to investigate the potential anticancer effect of a combination of iron oxide NPs loaded with 5-fluorouracil (5-FU) on the cell survival of the LS174T colon cancer cell line. 5-fluorouracil is a commonly used chemotherapy drug for treating various types of cancer, including colon cancer, and iron oxide NPs are known to be useful drug carriers for targeted drug delivery.

Nanoparticles were synthesized using the precipitation method, and X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM) analysis were conducted. Cells were cultivated in RPMI 1640 medium, and the MTT assay was carried out to assess cell viability after treatment with multiple components, including NP+drug. Quantitative polymerase chain reaction (qPCR) was carried out to assess the expression of apoptotic genes, including BAX, BAD, and BCL-2.

The MTT results showed that all components, especially NP+drug, had acceptable cytotoxic effects on cancer cells. The expression of pro-apoptotic genes was elevated, and the expression of the anti-apoptotic gene was decreased after treatment with the same components, especially NP+drug.

The results showed that all the studied components, especially drug-loaded NPs, have great cytotoxic and pro-apoptotic effects on colon cancer cells and can be considered colon cancer therapy.

 Silibinin, an herbal polyphenolic flavonolignan, has antioxidant and anticancer properties.

 This study aimed to evaluate some cellular and molecular effects of silibinin on the human ovarian cancer SKOV-3 cell line.

 For cytotoxicity investigations of silibinin, MTT assay was used at 24, 48, and 72 hours. Apoptosis and cell cycle were studied by flow cytometry. The effect of silibinin on mRNA expression of B-cell lymphoma 2 (Bcl-2), cyclin E, and S-phase kinase-associated protein 2 (SKP2) was determined by Quantitative reverse transcription polymerase chain reaction (QRT-PCR).

 Silibinin administration in lower concentrations (12.5 and 25 µg/mL) did not lead to significant (P < 0.05) changes in cell viability and even slightly increased cell growth after 72 hours. However, silibinin in higher concentrations (≥ 50µg/mL) inhibited SKOV-3 cell proliferation in a dose- and time-dependent manner. The mode of cell growth inhibition was apoptosis induction and G2/M cell cycle arrest. Silibinin caused down-regulation of the anti-apoptotic gene, namely Bcl-2. Additionally, silibinin resulted in down-regulation of the major genes in the cell cycle, including cyclin E and SKP2.

 Overall, this study confirmed the ability of silibinin to suppress ovarian cancer progression through the induction of apoptosis and inhibition of G2/M phase transition. Silibinin may be considered an efficient and safe herbal medication for ovarian cancer.

 Neuroblastoma (NB) is the most common solid childhood tumor with aggressive behavior and a high mortality rate. Multiple therapeutic approaches have been developed and applied to treat neuroblastoma, but resistance to therapies is inevitable, leading to treatment failure and cancer relapse. Therefore, perceiving the mechanisms of reduced drug sensitivity seems appropriate and promising in NB treatment to determine synergistic effects strategies like combination therapy.

 The present study aimed to investigate the modulation effect of the therapeutic efficacy of carboplatin (a chemotherapeutic agent) by co-administration of sialic acid (an alpha-keto acid sugar with a 9-carbon backbone located at the outermost end of N-linked and O-linked carbohydrate chains and in lipid-associated glycoconjugates showing aberrant expression in tumor cells caused tumor-genesis) in NB cells.

 In the present study, the effects of sialic acid, carboplatin, and Sia-Carbo (sialic acid in combination with carboplatin) were evaluated on viability and apoptosis using the determination of EC50 and IC50. Also, the capability of metastasis and apoptosis were assessed using real-time PCR. Moreover, the expression of MRP-1 encoded by ABCC1 (as a target for therapeutic suppression in high-risk neuroblastoma) was studied in different treatment groups.

 Regarding IC50 increasing carboplatin in the presence of sialic acid, the results showed that sialic acid treatment significantly modulated carboplatin's effect on cell apoptosis and induced ABCC1 expression. These findings show that sialic acid metabolic engineering can be a good approach to neuroblastoma therapy. It was suggested that targeting aberrant sialylation in combination with carboplatin exerts more profound apoptotic and anticancer effects on the neuroblastoma SH-SY5Y cell line than carboplatin monotherapy.