No abstract

The activation of Ca2+-permeable N-methyl-D-aspartic acid (NMDA) receptor channels (NMDARs) is crucial for the development and survival of neurons, but many cancers use NMDAR-mediated signaling as well, enhancing the growth and invasiveness of tumors. Thus, NMDAR-dependent pathways emerge as a promising target in cancer therapy. Here, we use the LN229 and U-87MG glioblastoma multiforme (GBM) cells and immunofluorescence staining of 53BP1 to analyze NMDAR-induced DNA double-strand breaks (DSBs), which represent an important step in the NMDAR signaling pathway in neurons by facilitating the expression of early response genes. Our results show that NMDAR activation leads to the induction of DSBs in a subpopulation of glioma cells. In a further analogy to neurons, our results demonstrate that the induction of DSBs in LN229 cells is dependent on the activity of topoisomerase IIβ (Top2β). Western blot analysis revealed that the inhibition of NMDARs, cAMP-responsive element binding transcription factor (CREB) and Top2β decreased the expression of the proto-oncogene cFos. Knockdown of Top2β with siRNAs resulted in a downregulation of cFos and increased the radiosensitivity of LN229 cells in clonogenic survival. We also observed impaired cFos expression upon NMDAR and Top2β inhibition in a primary GBM cell line, suggesting that NMDAR signaling may be widely used by GBMs, demonstrating the potential of targeting NMDAR signaling proteins for GBM therapy.

Solanum procumbens called ``Cà gai leo'' in Vietnam, belonged to the family of Solanaceae, which is a prickly diffuse, bright green perennial shrub, woody at the base. This plant has been sought for plenty of Vietnamese folk remedies for diseases such as rheumatism, back pain, detoxification, cough, pain relief, hemostasis, hepatitis, and cirrhosis. Chemical reports revealed the presence of lots of secondary metabolites such as steroids, triterpenoids, alkaloids, and phenolic compounds that have good biological activities such as antibacterial, antidiabetic, antioxidant, and antimicrobial... By column chromatography method together with thin layer normal-phase chromatography on the ethyl acetate extract of its entire plant, we isolated four compounds including dioscin (1), b -sitosterol (2), daucosterol (3) and 6'-O-acetyl-b -daucosterol (4). The result of theira-glucosidase inhibitory activity showed that compounds 2 and 4 had strong inhibition with IC50 values of 35.2 and 209.5 mM, comparing to the positive control, acarbose with an IC50 value of 214.5 mM. The results of this study have contributed to the scientific data of chemical compositions of Vietnamese medicinal plants, among them S. procumbens would potentially be developed as a plant-based drug to decrease the blood glucose level.

From the chloroform and ethyl acetate extracts of the leaves of Kalanchoe pinnata L. (Crassulaceae), two flavonoids and three phenolic compounds were isolated; named quercetin (1), 5,7,4’-trihydroxy-8,3’-dimethoxyflavone (2), gallic acid (3), ferulic acid (4) and isoferulic acid (5). Based on the NMR spectroscopy, their chemical structures were elucidated and the result was confirmed by comparison with published data.