TY  - JOUR
A1  - El-Hawary, Seham S.
A1  - Sayed, Ahmed M.
A1  - Mohammed, Rabab
A1  - Hassan, Hossam M.
A1  - Rateb, Mostafa E.
A1  - Amin, Elham
A1  - Mohammed, Tarek A.
A1  - El-Mesery, Mohamed
A1  - Bin Muhsinah, Abdullatif
A1  - Alsayari, Abdulrhman
A1  - Wajant, Harald
A1  - Anany, Mohamed A.
A1  - Abdelmohsen, Usama Ramadan
T1  - Bioactive brominated oxindole alkaloids from the Red Sea sponge Callyspongia siphonella
JF  - Marine Drugs
N2  - In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds 1 and 2) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of Callyspongia siphonella crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, Staphylococcus aureus (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and Bacillus subtilis (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in Pseudomonas aeruginosa (49.32% and 41.76% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds 1 and 2) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.
KW  - Callyspongia siphonella
KW  - LC-HRESIMS
KW  - metabolomic profiling
KW  - oxindole alkaloids
KW  - tisindoline
KW  - antibacterial
KW  - antibiofilm
KW  - antitrypanosomal
KW  - anticancer
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201485
VL  - 17
IS  - 8
ER  - 
TY  - JOUR
A1  - Lagler, Charlotte
A1  - El-Mesery, Mohamed
A1  - Kübler, Alexander Christian
A1  - Müller-Richter, Urs Dietmar Achim
A1  - Stühmer, Thorsten
A1  - Nickel, Joachim
A1  - Müller, Thomas Dieter
A1  - Wajant, Harald
A1  - Seher, Axel
T1  - The anti-myeloma activity of bone morphogenetic protein 2 predominantly relies on the induction of growth arrest and is apoptosis-independent
JF  - PLoS ONE
N2  - Multiple myeloma (MM), a malignancy of the bone marrow, is characterized by a pathological increase in antibody-producing plasma cells and an increase in immunoglobulins (plasmacytosis). In recent years, bone morphogenetic proteins (BMPs) have been reported to be activators of apoptotic cell death in neoplastic B cells in MM. Here, we use bone morphogenetic protein 2 (BMP2) to show that the "apoptotic" effect of BMPs on human neoplastic B cells is dominated by anti-proliferative activities and cell cycle arrest and is apoptosis-independent. The anti-proliferative effect of BMP2 was analysed in the human cell lines KMS12-BM and L363 using WST-1 and a Coulter counter and was confirmed using CytoTox assays with established inhibitors of programmed cell death (zVAD-fmk and necrostatin-1). Furthermore, apoptotic activity was compared in both cell lines employing western blot analysis for caspase 3 and 8 in cells treated with BMP2 and FasL. Additionally, expression profiles of marker genes of different cell death pathways were analysed in both cell lines after stimulation with BMP2 for 48h using an RT-PCR-based array. In our experiments we observed that there was rather no reduction in absolute cell number, but cells stopped proliferating following treatment with BMP2 instead. The time frame (48–72 h) after BMP2 treatment at which a reduction in cell number is detectable is too long to indicate a directly BMP2-triggered apoptosis. Moreover, in comparison to robust apoptosis induced by the approved apoptotic factor FasL, BMP2 only marginally induced cell death. Consistently, neither the known inhibitor of apoptotic cell death zVAD-fmk nor the necroptosis inhibitor necrostatin-1 was able to rescue myeloma cell growth in the presence of BMP2.
KW  - apoptosis
KW  - gene expression
KW  - necrotic cell death
KW  - multiple myeloma
KW  - cell metabolism
KW  - cell cycle and cell division
KW  - B cells
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158993
VL  - 12
IS  - 10
ER  -