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Epilepsy is associated with increased morbidity and mortality together and places a large financial burden on individuals and society. To evaluate the anticonvulsant action of protodioscin (PDSN) in experiments with animals with pilocarpine-induced convulsions. We assessed the activity of PDSN in pilocarpine induced seizures in combination with different agents which are acting via diverse receptors, such as atropine, memantine, nimodipine, diazepam, and flumazenil, to determine the exact receptors responsible for the action of PDSN. Furthermore, the level of antioxidant markers was investigated in the cerebellum and cerebral cortex in mice to define the antioxidant action of PDSN. The effects of PDSN on proapoptotic markers (i.e., Bcl-2, Bax, and caspase-3) was investigated via western blot analysis. PDSN significantly enhanced latency to the first convulsion and survival compared to the group treated with pilocarpine alone. Moreover, PDSN improved animal survival, and subjects experiencing no convulsions. Striatal glutamate and aspartate levels were not modified, and gamma amino butyric acid (GABA) levels increased, as a result of treatment with PDSN. The results suggest that the anticonvulsive action of PDSN is dependent on inhibitory amino acids. PDSN treatment also significantly decreased nitrite levels in the blood and brain cortex compared to the normal control. In the western blot analysis, PDSN exerted its neuroprotective effect via the upregulation of Bcl-2 and downregulation of Bax and caspase-3. The results of this study suggest that PDSN exerts neuroprotective effects via multiple mechanisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Multiple myeloma is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in multiple myeloma. Histone lysine methylation has emerged as a central epigenetic change in the organization of eukaryotic chromatin with far-reaching implications for the regulation of cell proliferation, cell-type differentiation, gene expression, genome stability, overall development, and genesis of cancer. Triptolide is the principal active ingredient in extracts from the Chinese herb Tripterygium wilfordii Hook.F (TwHF), and numerous studies have elucidated its antitumor property. Our experiments discovered that triptolide inhibited the proliferation of multiple myeloma cell line U266 in a time- and dose-dependent manner, induced G2/M cell cycle arrest and caspase-dependent apoptosis. Triptolide could decrease the expression of histone H3K4, H3K27 and H3K36 trimethylation in parallel with histone methyltransferases SMYD3, EZH2 and NSD1 respectively, which possibly was the anti-myeloma mechanism of triptolide., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Induction of apoptosis in tumor cells has become the major focus of anti-tumor therapeutics development. Juglone, a major chemical constituent of Juglans mandshurica Maxim, possesses several bioactivities including anti-tumor. Here, for the first time, we studied the molecular mechanism of Juglone-induced apoptosis in human leukemia HL-60 cells. In the present study, HL-60 cells were incubated with Juglone at various concentrations. Occurrence of apoptosis was detected by Hoechst 33342 staining and flow cytometry. Expression of Bcl-2 and Bax mRNA was determined by quantitative polymerase chain reaction (qPCR). The results showed that Juglone inhibits the growth of human leukemia HL-60 cells in dose- and time-dependent manner. Topical morphological changes of apoptotic body formation after Juglone treatment were observed by Hoechst 33342 staining. The percentages of Annexin V-FITC-positive/PI negative cells were 7.81%, 35.46%, 49.11% and 66.02% with the concentrations of Juglone (0, 0.5, 1.0 and 1.5 microg/ml). Juglone could induce the mitochondrial membrane potential (DeltaPsim) loss, which preceded release of cytochrome c (Cyt c), Smac and apoptosis inducing factor (AIF) to cell cytoplasm. A marked increased of Bax mRNA and protein appeared with Juglone treatment, while an evidently decreased of Bcl-2 mRNA and protein appeared at the same time. These events paralleled with activation of caspase-9, -3 and PARP cleavage. And the apoptosis induced by Juglone was blocked by z-LEHD-fmk, a caspase-9 inhibitor. Those results of our studies demonstrated that Juglone-induced mitochondrial dysfunction in HL-60 cells trigger events responsible for mitochondrial-dependent apoptosis pathways and the elevated ratio of Bax/Bcl-2 was also probably involved in this effect., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Gambogic acid (GA), the active ingredient from gamboges, has been verified as a potent anti-tumor agent in many cancer cells. Nevertheless, its function in lymphoma, especially in B-cell Non-Hodgkin lymphoma (NHL), remains unclear. Amplification and/or overexpression of steroid receptor coactivator-3 (SRC-3) have been detected in multiple tumors and have confirmed its critical roles in carcinogenesis, progression, metastasis and therapy resistance in these cancers. However, no clinical data have revealed the overexpression of SRC-3 and its role in B-cell NHL. In this study, we demonstrated the anti-tumor effects of GA, which included cell growth inhibition, G1/S phase cell cycle arrest and apoptosis in B-cell NHL. We also verified that SRC-3 was overexpressed in B-cell NHL in both cell lines and lymph node samples from patients. The overexpressed SRC-3 was a central drug target of GA, and its down-regulation subsequently modulated down-stream gene expression, ultimately contributing to apoptosis. Silencing SRC-3 decreased the expression of Bcl-2, Bcl-6 and cyclin D3, but not of NF-κB and IκB-α. GA treatment did not inhibit the activation of AKT signaling pathway, but induced the deacetylation of histone H3 at lysine 9 and lysine 27. Down-regulated SRC-3 was observed to interact with more HDAC1 to mediate the deacetylation of H3. As the component of E3 ligase, Cullin3 was up-regulated and mediated the degradation of SRC-3. Our results demonstrate that GA is a potent anti-tumor agent that can be used for therapy against B-cell NHL, especially against those with an abundance of SRC-3. [ABSTRACT FROM AUTHOR]

Abstract: Our previous study revealed that oroxylin A, a naturally occurring monoflavonoid isolated from Scutellariae radix, could inhibit the proliferation of human hepatocellular carcinoma HepG2 cells through inducing the apoptosis in these cells. However, the molecular mechanism of its anticancer activity remains poorly understood and warrants further investigations. In this study, we examined the anti-invasive activities of oroxylin A in vitro. The results showed that oroxylin A suppressed MDA-MB-435 cell adhesion to the fibronectin-coated substrate in a concentration-dependent manner. It inhibited the wound healing migration of MDA-MB-435 cells and invasion of MDA-MB-435 cells through reconstituted extracellular matrix (matrigel). Zymography revealed that oroxylin A decreased the secretion of matrix metalloproteinases-2 (MMP-2) and metalloproteinases-9 (MMP-9). Oroxylin A also inhibited the expressions of MMP-2 and MMP-9 in MDA-MB-435 cells. Additionally, oroxylin A exerted an inhibitory effect on the phosphorylation of extracellular regulated proteinkinases1/2 (ERK1/2). Collectively, these data provided a molecular basis for the antiinvasive effects of oroxylin A. Taken together, these findings strongly suggest that oroxylin A had potential anti-metastatic effect in vitro and shed light on the investigation of oroxylin A on breast cancer metastasis in vivo. [Copyright &y& Elsevier]