Synthesis of 3-(2-(subsituted-(trifluoromethyl)phenylamino)acetyl)-2H-chromen-2-one derivatives as new anticancer agents

Under solvent free conditions and in presence of a base 3-(2-(subsituted-(trifluoromethyl)phenylamino)acetyl)-2H-chromen-2-one derivatives were synthesized by grinding technique. Structural investigations were carried out with IR studies, HRMS, 1HNMR and 13CNMR. The compounds were checked for their in vitro anticancer activities against three different human cancer cell lines viz human breast cancer cell line (MCF-7), human cervical cancer cell line (HeLa) and human oral squamous cell carcinoma (SCC-40) using SRB method. All the title compounds showed low toxicity towards non-malignant PBMC cells indicating their tumour selectivity. The compounds exhibited good in vitro anti-proliferative potency at lower concentrations against HeLa and MCF-7 cell lines and remain moderately active against SCC-40.

miRNA Combinatorics and its Role in Cell State Control—A Probabilistic Approach

A hallmark of cancer evolution is that the tumor may change its cell identity and improve its survival and fitness. Drastic change in microRNA (miRNA) composition and quantities accompany such dynamic processes. Cancer samples are composed of cells’ mixtures of varying stages of cancerous progress. Therefore, cell-specific molecular profiling represents cellular averaging. In this study, we consider the degree to which altering miRNAs composition shifts cell behavior. We used COMICS, an iterative framework that simulates the stochastic events of miRNA-mRNA pairing, using a probabilistic approach. COMICS simulates the likelihood that cells change their transcriptome following many iterations (100 k). Results of COMICS from the human cell line (HeLa) confirmed that most genes are resistant to miRNA regulation. However, COMICS results suggest that the composition of the abundant miRNAs dictates the nature of the cells (across three cell lines) regardless of its actual mRNA steady-state. In silico perturbations of cell lines (i.e., by overexpressing miRNAs) allowed to classify genes according to their sensitivity and resilience to any combination of miRNA perturbations. Our results expose an overlooked quantitative dimension for a set of genes and miRNA regulation in living cells. The immediate implication is that even relatively modest overexpression of specific miRNAs may shift cell identity and impact cancer evolution.

CIC missense variants contribute to susceptibility for spina bifida

Neural Tube Defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to cerebral folate deficiency by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased risk for NTDs by depressing embryonic folate concentrations. In this study, we examined CIC variants from whole genome sequencing (WGS) data of 140 isolated spina bifida cases and identified 8 missense variants of CIC gene. We tested the pathogenicity of the observed variants through multiple in vitro experiments. We determined that CIC variants decreased FOLR1 protein level and planar cell polarity (PCP) pathway signaling in a human cell line (HeLa). In a murine cell line (NIH3T3), CIC loss of function variants down regulated PCP signaling. Taken together, this study provides evidence supporting CIC as a risk gene for human NTD.

The effect of Chaihu-shugan-san on cytotoxicity induction and PDGF gene expression in cervical cancer cell line HeLa in the presence of paclitaxel +cisplatin

Chaihu-shugan-san, as a traditional Chinese herbal formula, is composed of seven different herbs. This medicine can treat cancer due to its antioxidant compounds. In this study, the effect of Chaihu-shugan-san was considered on cytotoxicity induction and PDGF gene expression in cervical cancer cell line HeLa at different concentrations and at different times, by the MTT method. Paclitaxel + cisplatin were used as a control in this study. The expression of the PDGF gene was quantitatively evaluated in treated cells by real-time PCR, and a generalized linear model was used to evaluate the effect of the medicine, and Duncan's multiple range tests were used to evaluate the data. The results of the MTT test showed that Chaihu-shugan-san had antitumor properties in different concentrations, but there was a significant difference between this medicine and paclitaxel +cisplatin. Also, examination of gene expression showed that this medicine reduced the expression of the PDGF gene in the HeLa cancer cell line (P ? 0.04). Therefore, Chaihu-shugan-san could be suggested as an effective factor in preventing the growth of cervical cancer cells and controlling angiogenic factors that play an important role in the metastasis of cancerous tumors.

The Extensive and Expensive Impacts of HEp-2 [HeLa], Intestine 407 [HeLa], and Other False Cell Lines in Journal Publications

Cell lines are essential models for biomedical research. However, they have a common and important problem that needs to be addressed. Cell lines can be misidentified, meaning that they no longer correspond to the donor from whom the cells were first obtained. This problem may arise due to cross-contamination: the accidental introduction of cells from another culture. The contaminant, which is often a rapidly dividing cell line, will overgrow and replace the original culture. The end result is a false cell line, also known as a misidentified or imposter cell line. False cell lines may come from an entirely different species, tissue, or cell type than the original donor. If undetected, false cell lines produce unreliable and irreproducible results that pollute the biomedical literature and threaten the development of reliable drug discovery and meaningful patient treatments. The goal of this study was to ascertain how widespread this problem is and how it affects the literature, as well as to estimate how much funding has been used to produce pools of scientific literature of questionable value. We focus on HEp-2 [HeLa] and Intestine 407 [HeLa], two false cell lines that are widely used in the scientific literature but were shown to be cross-contaminated in 1967. These two cell lines have been used in 8497 and 1397 published articles and extensively described as laryngeal cancer and normal intestine, respectively, rather than their true identity: the cervical cancer cell line HeLa. Discussed are tools, approaches, and resources that can address this issue—both retrospectively and prospectively.

One-pot synthesis and biological evaluation of novel 3-(5-((aryl) methyl) isoxazol-3-yl)-4H-chromen-4-one derivatives as potent antibacterial and anticancer agents

In search of better antibacterial and anticancer agents, a series of novel 3-(5-((aryl) methyl) isoxazol-3-yl)-4Hchromen- 4-one derivatives was synthesized (4a-4l) by using 4-oxo-4H-chromene-3-carbaldehyde and alkyne via in situ generated nitrile oxide and evaluated for their antibacterial and anticancer activity in vitro. Antibacterial activity was evaluated against three G+ bacterial strains and anticancer activity against breast cancer cell line (MCF-7) and cervical carcinoma cell line (HeLa). Among all the tested compounds, 4j and 4g exhibited potent antibacterial activity against tested grampositive bacterial strains. 4g, 4i and 4j exhibited potent cytotoxic activity against MCF-7 with IC50 values nearer to the standard drug doxorubicin.

Stingless Bee Honey and Honeybee Honey Characteristics in Relation to Anticancer Potential

Introduction: The composition of the honey depends on the intrinsic and extrinsic factors, including place of origin, the floral types, the season and the storage conditions. This study compared the anticancer potential, quality, antioxidant and phytochemical between unprocessed stingless bee honey (SBH) and honeybee honey (HBH) from the same environmental factors including place of nest, floral type (Acacia), harvesting month (August) and storage conditions (<5°C). Materials and methods: To measure quality, 5-hydroxymethylfurfural (HMF) and diastase activity were determined, followed by total phenolic content (TPC) and total flavonoid content (TFC) for phytochemicals. Antioxidant activity was assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cytotoxicity towards cervical cancer cell line (HeLa) was measured using a 2-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay (IC50). Results: The results indicated that HBH exhibited significantly higher diastase activity (2.17 ± 0.07 DN), TPC (338.95 ± 3.49 mg GAE/kg), DPPH scavenging activity EC50 (80.06 mg/ml) and MTT activity IC50 (64.80 mg/ml) towards HeLa as compared to SBH with absence of diastase activity, TPC (250.60 ± 3.98 mg GAE/kg), DPPH scavenging activity EC50 (165.80 mg/ml) and MTT activity IC50 (75.76 mg/ml). However, there were no significant differences in HMF and TFC between HBH and SBH. Conclusion: Therefore, the present study found that HBH demonstrates better antioxidant capacity, anticancer potential and phenolic content as compared to SBH.

Chemical compositions, antibacterial, antifungal and cytotoxic effects of Alhagi mannifera five extracts

Objectives Plants were used as medicines thousands of years ago. Conventional medicine use is increasing and many of the currently used drugs are extracted from herbal sources. In Palestinian traditional medicine, the Alhagi mannifera plant is used for the treatment of cancer. Our study aimed to extract this plant using five solvent fractions, identifying their chemical compositions, and evaluating their antimicrobial and cytotoxic effects. Methods The successive technique was used to extract five solvent fractions of A. mannifera. While the spectral analysis was used to characterize quantitatively and qualitatively the chemical components of these extracts. The antimicrobial activity of plant extracts was evaluated against seven microbial strains using a broth micro-dilution assay. The cytotoxic activity was assessed using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay against cervical cancer cell line (HeLa). Results A total of 165 compounds were identified in A. mannifera different extracts. In the petroleum ether extract were found a total of 55 compounds. The major compounds were 2,5-cyclooctadien-1-ol (9.42%), 3-chloropropionic acid, heptyl ester (9.42%), carbonic acid, ethyl nonyl ester (9.42%) and chloroacetic acid. In methylene chloride extract a total of 11 compounds were found, and the major compounds were m-ainobenzenesulfonyl fluoride (14.35%), dodecane,2,6,10-trimethyl- (14.35%) and propanoic acid,2,2-dimethyl-,2-ethylexyl ester (14.35%). In chloroform extract, a total of 23 compounds were found. The major compounds were 5-ethyl-1-nonene (21.28%), and decanedioic acid, bis(2-ethylhexyl) ester (21.28%). In acetone extract were found a total of 47 compounds and the major compound was phenol,2,4-bis(1,1-dimethylethyl)- (5.22%). In methanol extract a total of 29 compounds were found and the major compounds were 3-o-methyl-d-glucose (10.79%), myo-inositol, 2-c-methyl- (10.79%), myo-inositol, 4-c-methyl- (10.79%), and scyllo-inositol,1C-methyl- (10.79%). All extracts showed antimicrobial activity. However, the petroleum ether extract showed the most potent antimicrobial effect against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, MRSA, and Candida albicans with minimal inhibitory concentration (MIC) values of 1.25, 1.25, 6.25, 0.325, 6.25, and 1.56 μg/mL, respectively. De facto, chloroform extract followed by ether extract displayed potential cytotoxic activity with IC50 values of 0.2 and 1.2 mg/mL, respectively. Conclusions A. mannifera was found to contain a variety of phytochemicals and its chloroform extract showed a potent cytotoxic effect on HeLa cancer cells. In addition, petroleum ether showed potent antimicrobial agents and these extracts look promising as drug candidates. Further in vivo investigations should be conducted to provide the basis for developing new cancer and microbial infections treatments.