Cryptolepine Suppresses Colorectal Cancer Cell Proliferation, Stemness, and Metastatic Processes by Inhibiting WNT/ß-Catenin Signaling.

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths globally. Evidence shows that over 90% of CRC cases are initiated by a deregulated Wingless Integrated Type-1 (WNT)/ß-catenin signaling pathway. The WNT/ß-catenin pathway also promotes CRC cell proliferation, stemness, and metastasis. Therefore, modulators of the WNT/ß-catenin pathway may serve as promising regimens for CRC. This study investigated the effect of cryptolepine-a plant-derived compound-on the WNT/ß-catenin pathway in CRC. Two CRC cell lines, COLO205 and DLD1, were treated with cryptolepine or XAV 939 (a WNT inhibitor) in the presence or absence of WNT3a (a WNT activator). Using a tetrazolium-based assay, cryptolepine was found to reduce cell viability in a dose- and time-dependent manner and was a more potent inhibitor of viability than XAV 939. RT-qPCR analyses showed that cryptolepine reverses WNT3a-induced expression of ß-catenin, c-MYC, and WISP1, suggesting that cryptolepine inhibits WNT3a-mediated activation of WNT/ß-catenin signaling. Cryptolepine also repressed WNT3a-induced OCT4 and CD133 expression and suppressed colony formation of the cells, indicating that cryptolepine inhibits the stemness of CRC cells. Additionally, cryptolepine inhibited WNT3a-induced epithelial-to-mesenchymal transition by reducing the expression of SNAI1 and TWIST1 genes. In a wound healing assay, cryptolepine was found to suppress cell migration under unstimulated and WNT3a-stimulated conditions. Moreover, cryptolepine downregulated WNT3a-induced expression of MMP2 and MMP9 genes, which are involved in cancer cell invasion. Altogether, cryptolepine suppresses CRC cell proliferation, stemness, and metastatic properties by inhibiting WNT3a-mediated activation of the WNT/ß-catenin signaling pathway. These findings provide a rationale for considering cryptolepine as a potential WNT inhibitor in CRC.

Risk of Heavy Metal Poisoning From Consuming Grasscutter Digesta in Ghana.

Grasscutter (cane rat/Thryonomys swinderianus) digesta is used as a spice in Ghana. Research shows that heavy metals from the environment may accumulate in the internal organs of grasscutters, which raises concerns about the possible contamination of grasscutter digesta, too, with heavy metals. Although grasscutter meat in Ghana has been described as safe for consumption, information is lacking on the health risks associated with ingesting the digesta. This study, therefore, aimed to assess the knowledge and perceptions of a merchant and a consumer about the safety of ingesting grasscutter digesta and to evaluate potential health risks from exposure to heavy metals from the spice. A total of 12 digesta samples were analyzed to evaluate potential health risks from exposure to Cd, Fe, Hg, and Mn using a Varian AA240FS Atomic Absorption Spectrometer. The levels of Cd, Hg, and Mn were below the detection limit of 0.01 mg/kg digesta. Also, the estimated daily intake of Fe (0.02 mg/kg) was less than the maximum allowable dose recommended by the US EPA (0.7 mg/kg). The hazard indices of Fe for daily and weekly consumption were <1, suggesting that the consumers may be safe from iron poisoning. Because grasscutter digesta is a relatively expensive spice, it is unlikely to be consumed daily by the average Ghanaian. Moreover, if 10 g of digesta is consumed daily, it can be safely ingested about 971 times in a month. Domestication of grasscutters may be a useful approach to monitor their diet and consequently the quality of their digesta.

Cassava microfiber-reinforced gelatin scaffold holds promise for tissue engineering by exhibiting cytocompatibility with HEK 293 cells.

Cellulose fiber-reinforced composite scaffolds have recently become an interesting target for biomedical and tissue engineering (TE) applications. Cassava bagasse, a fibrous solid residue obtained after the extraction of cassava starch and soluble sugars, has been explored as a potential source of cellulose and has been successfully used to enhance the mechanical properties of gelatin scaffolds for TE purposes. This study assessed the cytocompatibility of the cassava microfiber-gelatin composite scaffold using human embryonic kidney cells (HEK 293) and a breast cancer cell line (MDA MB 231) under ISO 10993-5 standards. The viability of cells within the composite scaffold was analyzed through MTT assay. The growth of HEK 293, as well as the cell morphology, was not affected by the presence of cellulose within the composite, whereas the growth of breast cancer cells appeared to be inhibited with noticeable changes in cell morphology. These findings suggest that the presence of the cassava fiber in gelatin is not cytotoxic to HEK 293 cells. Thus, the composite is suitable for TE purposes when using normal cells. On the contrary, the presence of the fiber in gelatin elicited a cytotoxic effect in MDA MB 231 cells. Thus, the composite may not be considered for three-dimensional (3D) tumor cell studies requiring cancer cell growth. However, further studies are required to explore the use of the fiber from cassava bagasse for its anticancer cell properties, as observed in this study.

Inverse Comorbidity between Down Syndrome and Solid Tumors: Insights from In Silico Analyses of Down Syndrome Critical Region Genes.

An inverse comorbidity has been observed between Down syndrome (DS) and solid tumors such as breast and lung cancers, and it is posited that the overexpression of genes within the Down Syndrome Critical Region (DSCR) of human chromosome 21 may account for this phenomenon. By analyzing publicly available DS mouse model transcriptomics data, we aimed to identify DSCR genes that may protect against human breast and lung cancers. Gene expression analyses with GEPIA2 and UALCAN showed that DSCR genes ETS2 and RCAN1 are significantly downregulated in breast and lung cancers, and their expression levels are higher in triple-negative compared to luminal and HER2-positive breast cancers. KM Plotter showed that low levels of ETS2 and RCAN1 are associated with poor survival outcomes in breast and lung cancers. Correlation analyses using OncoDB revealed that both genes are positively correlated in breast and lung cancers, suggesting that they are co-expressed and perhaps have complementary functions. Functional enrichment analyses using LinkedOmics also demonstrated that ETS2 and RCAN1 expression correlates with T-cell receptor signaling, regulation of immunological synapses, TGF-ß signaling, EGFR signaling, IFN-γ signaling, TNF signaling, angiogenesis, and the p53 pathway. Altogether, ETS2 and RCAN1 may be essential for the development of breast and lung cancers. Experimental validation of their biological functions may further unravel their roles in DS and breast and lung cancers.

Antiproliferative Activities of Methanolic Extract and Fractions of Tetrapleura Tetraptera Fruit.

Most of the current cancer chemotherapeutics are associated with harsh and undesirable side effects, including toxicity and chemoresistance, driving the need for safer and more effective alternatives. In this study, the antiproliferative activities of the methanolic extract of Tetrapleura tetraptera fruits and nine different fractions (C1-C9) from the column chromatographic separation of the extract against leukemia (Jurkat) and human breast cancer (MCF-7) cell lines were investigated using a tetrazolium-based colorimetric assay. Phytochemical screening of the extract and fractions found alkaloids, carbohydrates, flavonoids, glycosides, phenols, saponins, steroids, tannins, and terpenoids in the methanolic extract. Most of the fractions exhibited antiproliferative activity (>100 µg/mL) with the Jurkat cells being more susceptible than the MCF-7 cells. Four of the collected fractions C4, C3, C5, and C2 had good selective indices in decreasing order of activity, in the case of Jurkat cells. Liquid chromatography-mass spectrometry analysis of all samples (except for C4 and C9) revealed that C1, C2, C3, and C5 each had a single component. More importantly, fractions C2, C3, and C5, which were selective to Jurkat cells, also had the same retention time of 1.846 min. Fractions C6 and C8 had two components, with C7 having four components. This study serves as a basis for further work to isolate and characterize potential anticancer agents from the fractions of extracts of T. tetraptera fruits.

Extremely low-frequency electromagnetic field induces neural differentiation of hBM-MSCs through regulation of (Zn)-metallothionein-3.

Extremely low-frequency electromagnetic field (ELFEMF) can stimulate neural differentiation in human bone marrow-derived mesenchymal cells (hBM-MSCs), and this provides an opportunity for research on neurodegenerative diseases such as Alzheimer's disease (AD). Metallothionein-3 (MT3), an isoform of the metal-binding proteins, metallothioneins, involved in maintaining intracellular zinc (Zn) homeostasis and the deregulation of zinc homeostasis, has separately been implicated in AD. Here, we investigated the effect of ELFEMF-induced neural differentiation of hBM-MSCs on Zn-MT3 homeostatic interaction. Exposure to ELFEMF induced neural differentiation of hBM-MSCs, which was characterized by decreased proliferation and enhanced neural-like morphology. We observed expression of neuronal markers such as ß-tubulin3, pleiotrophin, and neurofilament-M at the mRNA level and MAP2 at the protein level. ELFEMF-induced neural differentiation correlated with decreased expression of metal-response element-transcription factor 1 and MT3, as well as decreased intracellular Zn concentration. In addition, upregulation of dihydropyrimidinase-related protein 2 was observed, but there was no change in γ-enolase expression. These data indicate a possible regulatory mechanism for MT3 during neural differentiation. Our findings provide considerable insight into molecular mechanisms involved in neural differentiation, which is useful for developing new treatments for neurodegenerative diseases. Bioelectromagnetics. 38:364-373, 2017. © 2017 Wiley Periodicals, Inc.