Biosynthesis Zinc Oxide Nanoparticles Using Senna Occidentalis Leaf Extract and Evaluation of their Cytotoxic Effect on SW480 Colon Cancer Cell Line

ObjectiveIn the present study, we green synthesized ZnO NPs (zinc oxide nanoparticles) from Senna occidentalis leaf extract which were subsequently assessed for their cytotoxic and antioxidant activity on colon cancer SW480 cell line.Results Zinc oxide nanoparticles were characterized by using UV-Vis spectroscopy, X-ray diffractometer (XRD), Particle size analyzer (PSA), Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FE-SEM), Energy-dispersive X-ray (EDS) and atomic force microscope (AFM) analysis. The PSA, XRD and AFM showed 20-50 nm size and nearly cuboidal and irregular shaped of the ZnO NPs. The synthesized ZnO nanoparticles were evaluated for their anticancer activity on human colon cancer cell line (SW480) by using MTT and neutral red uptake assay. The SW480 colon cancer cells were treated with various concentrations of ZnO NPs in the range of 20–100 µg/ml for 2 hrs. The result showed that ZnO NPs could reduce cell viability of SW480 cells up to 50% at the concentration of 100 µg/ml and induce membrane leakage in a concentration dependent manner.ConclusionThe anticancer activity of zinc oxide nanoparticles has showed that these can be used as effective anti-cancer agent against colon cancer cell lines (SW480).

Mitotic spindle formation in the absence of Polo kinase

Mitosis is a fundamental process in every eukaryote, in which chromosomes are segregated into two daughter cells by the action of the microtubule (MT)-based spindle. Despite this common principle, genes essential for mitosis are variable among organisms. This indicates that the loss of essential genes or bypass-of-essentiality (BOE) occurred multiple times during evolution. While many BOE relationships have been recently revealed experimentally, the BOE of mitosis regulators (BOE-M) has been scarcely reported and how this occurs remains largely unknown. Here, by mutagenesis and subsequent evolutionary repair experiments, we isolated viable fission yeast strains that lacked the entire coding region of Polo-like kinase (Plk), a versatile essential mitotic kinase. The BOE of Plk was enabled by specific mutations in the downstream machinery, including the MT-nucleating gamma-tubulin complex, and more surprisingly, through downregulation of glucose uptake, which is not readily connected to mitosis. The latter bypass was dependent on casein kinase I (CK1), which has not been considered as a major mitotic regulator. Our genetic and phenotypic data suggest that CK1 constitutes an alternative mechanism of MT nucleation, which is normally dominated by Plk. A similar relationship was observed in a human colon cancer cell line. Thus, our study shows that BOE-M can be achieved by simple genetic or environmental changes, consistent with the occurrence of BOE-M during evolution. Furthermore, the identification of BOE-M constitutes a powerful means to uncover a hitherto under-studied mechanism driving mitosis and also hints at the limitations and solutions for selecting chemotherapeutic compounds targeting mitosis.

Selective Anticancer and Antimicrobial Metallodrugs Based on Gold(III) Dithiocarbamate Complexes

New dithiocarbamate cycloaurated complexes have been synthesized and their physicochemical and in vitro antitumor properties have been evaluated. All the performed studies highlighted good transport through the blood and biodistribution, according to the balance between the properties of hydrophilicity/lipophilicity and the binding of moderate strength to the BSA protein. Furthermore, none of the complexes exhibited reduction or decomposition reactions, presenting excellent physiological stability. The in vitro cytotoxic effect was evaluated on human colon cancer cell line Caco-2/TC7, and the complexes showed great antiproliferative activity and excellent selectivity, as much less effect was detected on normal Caco-2/TC7 cells. Most of the complexes exhibit antiproliferative activity that was better than or similar to auranofin, and at least nine times better than that of cisplatin. Its action mechanism is still under discussion since no evidence of cell cycle arrest was found, but an antioxidant role was shown for some of the selective complexes. All complexes were also tested as antimicrobial drugs, exhibiting good activity towards S. aureus and E. coli. bacteria and C. albicans and C. neoformans fungi.

The Expression And The Tumor Suppressor Role of CLDN6 In Colon Cancer

As a member of the tight junction family, CLDN6 is a tumor suppressor gene in breast cancer, but its role in colon cancer is unknown. In this research, we aimed at revealing the function of CLDN6 in colon cancer. We found that CLDN6 expressed lower in colon cancer tissues compared with adjacent normal tissues and the low expression of CLDN6 was correlated with lymph node metastasis. Similarly, CLDN6 expressed lower in the colon cancer cell line SW1116 compared with the normal human colon epithelial cell line NCM460. Upon CLDN6 overexpression in SW1116 cells, the proliferation of cells was suppressed in vitro and in vivo. Consistently, the migration and invasion abilities of cells were significantly inhibited after CLDN6 overexpression. Furthermore, the TYK2/STAT3 pathway was activated in SW1116/CLDN6 cells, and inhibition of this pathway with AG490 reversed the inhibition of migration and invasion of SW1116 cells by CLDN6. Therefore, our data indicated that CLDN6 acted as a tumor suppressor and had the potential to be regarded as a biomarker for the progression of colon cancer.

The Effect of Fertilized Egg White on Growth, Migration, Differentiation and Genes Expression Profile in SW480 Colon Cancer Cell Line

Background: Embryonic microenvironments influence cancer stem cells properties, which leads to anti-cancer effects. Therefore, the current study investigates the effects of fertilized egg white, as an embryonic/fetal microenvironment, on survival, apoptosis, self-renewal characteristic, stemness properties, and migration capacity of SW480 colon cancer cells and 5-fluorouracil (5FU) resistant subgroup.Methods: MTT and Flow cytometry was used to study the cell viability and cell cycle analysis. Clonogenic, spheroid formation, and wound healing assays were used to evaluate cancer cells' self-renewal, stemness properties, and migration capacity. RT-PCR was performed to analyze NANOG, c-MYC, E-cadherin, and NDRG1 mRNA expression.Results: The SW480 colon carcinoma cell line and SW480-5FU chemo-resistant subpopulation cells were subjected to Fertilized Egg White (FEW). FEW decreased cell viability and increased the percentage of the sub-G1 stage in both cell lines. In addition, colony and spheroid formations were decreased in both cells, and the FEW inhibited the migration. Expression of NANOG and c-MYC were reduced in both cells. E-cadherin and NDRG1 expression increased in SW480 cells.Conclusion: FEW decreased the SW480 colon cancer cell line and the SW480-5FU chemo-resistant subpopulation growth and migration. Also, by the changes observed in gene expression and spheroid formation, we suggest the possibility of decreased stemness properties and induction of differentiation following fertilized egg white treatment.

Virtual Screening for Biomimetic Anti-Cancer Peptides from Cordyceps militaris Putative Pepsinized Peptidome and Validation on Colon Cancer Cell Line

Colorectal cancer is one of the leading causes of cancer-related death in Thailand and many other countries. The standard practice for curing this cancer is surgery with an adjuvant chemotherapy treatment. However, the unfavorable side effects of chemotherapeutic drugs are undeniable. Recently, protein hydrolysates and anticancer peptides have become popular alternative options for colon cancer treatment. Therefore, we aimed to screen and select the anticancer peptide candidates from the in silico pepsin hydrolysate of a Cordyceps militaris (CM) proteome using machine-learning-based prediction servers for anticancer prediction, i.e., AntiCP, iACP, and MLACP. The selected CM-anticancer peptide candidates could be an alternative treatment or co-treatment agent for colorectal cancer, reducing the use of chemotherapeutic drugs. To ensure the anticancer properties, an in vitro assay was performed with “CM-biomimetic peptides” on the non-metastatic colon cancer cell line (HT-29). According to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results from peptide candidate treatments at 0–400 µM, the IC50 doses of the CM-biomimetic peptide with no toxic and cancer-cell-penetrating ability, original C. militaris biomimetic peptide (C-ori), against the HT-29 cell line were 114.9 µM at 72 hours. The effects of C-ori compared to the doxorubicin, a conventional chemotherapeutic drug for colon cancer treatment, and the combination effects of both the CM-anticancer peptide and doxorubicin were observed. The results showed that C-ori increased the overall efficiency in the combination treatment with doxorubicin. According to the acridine orange/propidium iodine (AO/PI) staining assay, C-ori can induce apoptosis in HT-29 cells significantly, confirmed by chromatin condensation, membrane blebbing, apoptotic bodies, and late apoptosis which were observed under a fluorescence microscope.

A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy

An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing the Quality by Design (QbD) concept, as a means to enhance the antiproliferative effect of the co-formulation on C26 murine colon cancer cells co-cultured with macrophages. It is known that the quality profile of liposomes is dependent on the critical quality attributes (CQAs) of liposomes (drug entrapped concentration, encapsulation efficiency, size, zeta potential, and drug release profile), which are, in turn, directly influenced by various formulation factors and processing parameters. By using the design of experiments, it was possible to outline the increased variability of CQAs in relation to formulation factors and identify by means of statistical analysis the material attributes that are critical (phospholipids, DOX and SIM concentration) for the quality of the co-formulation. The in vitro studies performed on a murine colon cancer cell line highlighted the importance of delivering the optimal drug ratio at the target site, since the balance antiproliferative vs. pro-proliferative effects can easily be shifted when the molar ratio between DOX and SIM changes.

Anticancer Activity Assay of Nano-Fractional Compounds that Purified from Soil Actinomycetes

Background and objectives: Cancer remains a global problem of health, and has been recorded as one of the causes of death after heart disease Natural products from plants, the environment and microorganisms are leveraged for the purpose of fighting cancer. Actinobacteria have been recognized as main sources of bioactive natural products as early as in the 1950s, for which about half of the secondary metabolites revealed, including enzymes, antibiotics, immunosuppressive, and anti-tumour agents Materials and methods:The methods of this study included isolated and identification of bacteria from soil samples and identified by morphology characters and biochemical test. Subjected extract of actinomycetes to HPLC purification then collected purified fractions then analyzed by GC-mass. After the fractions were mixed with liposome nanoparticals which tested activity on HT29 colon cancer cell line. Results: The results of identification of bacterial isolates showed the colonies growing on a SNA medium were morphologically identified where the colonies were well-growth and had a gray color, not producing dyes in the medium. The results of the biochemical tests indicated that isolates were amylase, catalase, and gelatinase producing isolates and non-lipase producing, non H2S production and consuming urea, while the carbon consumption test indicated the isolates' ability to consume starch, glucose and sucrose respectively. While The results of preparative HPLC revealed that 4 fractions analytical HPLC with (50 % HPLC-grade acetonitrile) at 254 nm and cycling up was employed to increase the separation efficiency. The chemical composition of the HPLC fractions using GC-MS showed the identification of many components example ( Hexadeconic acid , Octadecanoic acid,ethyl ester and Fumaric acid). The results of In vitro anti-tumor cytotoxicity showed that all four nano purified fractions were applied on HT 29 colon cancer cells and exhibited significantly differences compared with control.