Antimicrobial peptide moricin induces ROS mediated caspase-dependent apoptosis in human triple-negative breast cancer via suppression of notch pathway.

BACKGROUND: Breast cancer is the world's most prevalent cancer among women. Microorganisms have been the richest source of antibiotics as well as anticancer drugs. Moricin peptides have shown antibacterial properties; however, the anticancer potential and mechanistic insights into moricin peptide-induced cancer cell death have not yet been explored. METHODS: An investigation through in silico analysis, analytical methods (Reverse Phase-High Performance Liquid Chromatography (RP-HPLC), mass spectroscopy (MS), circular dichroism (CD), and in vitro studies, has been carried out to delineate the mechanism(s) of moricin-induced cancer cell death. An in-silico analysis was performed to predict the anticancer potential of moricin in cancer cells using Anti CP and ACP servers based on a support vector machine (SVM). Molecular docking was performed to predict the binding interaction between moricin and peptide-related cancer signaling pathway(s) through the HawkDOCK web server. Further, in vitro anticancer activity of moricin was performed against MDA-MB-231 cells. RESULTS: In silico observation revealed that moricin is a potential anticancer peptide, and protein-protein docking showed a strong binding interaction between moricin and signaling proteins. CD showed a predominant helical structure of moricin, and the MS result determined the observed molecular weight of moricin is 4544 Da. An in vitro study showed that moricin exposure to MDA-MB-231 cells caused dose dependent inhibition of cell viability with a high generation of reactive oxygen species (ROS). Molecular study revealed that moricin exposure caused downregulation in the expression of Notch-1, NF-ƙB and Bcl2 proteins while upregulating p53, Bax, caspase 3, and caspase 9, which results in caspase-dependent cell death in MDA-MB-231 cells. CONCLUSIONS: In conclusion, this study reveals the anticancer potential and underlying mechanism of moricin peptide-induced cell death in triple negative cancer cells, which could be used in the development of an anticancer drug.

Anagallis arvensis Induces Apoptosis in HL-60 Cells Through ROS-Mediated Mitochondrial Pathway.

The present study was taken up to evaluate the apoptosis inducing ability of alcoholic extract of whole plant of Anagallis arvensis (AAE) in HL-60 cells. We observed time and concentration dependent decrease in cell viability after treatment with AAE. Fluorescent staining and scanning electron micrographs of treated HL-60 cells demonstrated chromatin condensation, nuclear fragmentation and formation of apoptotic blebs. There was a marked increase in hypodiploid population of cells as observed by cell cycle analysis. Annexin V-FITC/PI also depicted the presence of apoptotic cells. Anti-apoptotic protein Bcl-2 was observed to be decreased by 62% at 20 µg/ml concentration and a significant increase in ROS production up to 6.9-fold was observed in time dependent manner. In addition, alteration in mitochondrial membrane potential was observed, which was followed by cytochrome c release to cytoplasm. Activated levels of mitochondrial downstream pathway protein namely Caspase-3 and 9, were detected in treated HL-60 cells by colorimetric analysis. DNA ladder formation, a biochemical hallmark of apoptosis was also observed in treated HL-60 cells. The results of the present study support the apoptotic potential of AAE and probability of its promising role in development as effective anticancer agent against leukemia cells.

Spectrum of tuberculosis in dialysis patients in saudi arabia.

Data from different regional hospitals of Saudi Arabia were collected to know the prevalence, clinical features and results of therapy of tuberculosis, in patients on dialysis. Eight hospitals located in five different provinces of Saudi Arabia were involved. There were 132 patients with TB on dialysis of whom 75 were males (mean ages in different hospitals ranging 42-58 years) and 57 were females (mean ages ranging 38-58 years). The prevalence of TB in these patients varied from 2.4 to 14.5% with an average of 7%, which is 12 times commoner than in the general population of Saudi Arabia. The presenting clinical features were fever (65%), cough (17%), weight loss (59%) and anorexia (58%). The organs/systems involved by TB were pulmonary in 73 (55.3%), lymphadenopathy in 30 (22.7%) peritoneal in 27 (20.4%) and bone in seven (5.3%). The diagnosis of TB was made by X-ray chest in 73, positive acid fast bacilli in sputum in 38, lymph node biopsy in 30, ascitic fluid examination in 20 and other tests in 17 patients. Four anti-TB drugs namely, isoniazid (INH), rifampicin (Rif), ethambutol (Eth) and pyrazinamide (Pyra) were used in 58 patients (44%) for six months; three drugs namely, INH, Rif, and Eth or Pyra were used in 61 patients (46%) for a variable period of six to 12 months. A total of 28 (21%) patients expired, eight while on therapy, one before starting the therapy and 19 after they were cured of TB. The main causes of death were sepsis in eight (28.5%), cardiovascular in seven (25%) and sudden death in six (21%). TB was not the direct cause of death in any of the patients except one, in whom it could be contributory.