DNA damage induced by ionizing radiation (IR) activates p53, leading to the regulation of downstream pathways that control cell-cycle progression and apoptosis. However, the mechanisms for the IR-induced p53 activation and the differential activation of pathways downstream of p53 are unclear. Here we provide evidence that the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) serves a...

In cultured HEK, we observed that HD (0.3-1.0 mM)-induced DNA damage triggers DNA repair and apoptosis, which may be interdependent. We studied the effects of a general caspase inhibitor, Z-VADfmk (0.004 mM) and the Fas (CD95) receptor (induces apoptosis on Fas ligand binding) antibody on DNA damage and its repair in HD-exposed HEK. Both Z-VAD-fmk and the CD95 antibody reduced HD-induced DNA de...

Background: Calotropis gigantea (family: Asclepiadaceae) has been known to contain cardiac glycosides. The C. gigantea extracts have been reported as cytotoxic to a few cancer cell lines. The present study was designed to examine the effect of Calotropis gigantea methanolic extract (CGME) on the growth and apoptosis in human breast carcinoma cell line (MCF-7 cells).Methods: The study was ...

Infected cells recognize viral replication as a DNA damage stress and elicit a DNA damage response that ultimately induces apoptosis as part of host immune surveillance. Here, we demonstrate a novel mechanism where the murine gamma herpesvirus 68 (gammaHV68) latency-associated, anti-interferon M2 protein inhibits DNA damage-induced apoptosis by interacting with the DDB1/COP9/cullin repair compl...

Today’s medical word is highly dependent on severel natural products (e.g. taxol) in fighting different kinds of cancer and in constantly working to found new compounds. In this respect, 3-hydrogenkwadaphnin is a new diterpene ester isolated from Dendrostellera lessertii (Thymelaceae). It has been previously shown that this new compound has high anti-tumor activity and the capability of arresti...

Background: Cytoplasm and mitochondria are considered as the major origins of sperm ROS production. Sperm is prone to DNA damage by exposure to ROS or due impaired chromatin remodeling or low DNA protamination. Therefore, the aim of this study was to see if there is any association between impaired chromatin packaging and origin of ROS production. Materials and Methods: Cytosolic ROS, mitochond...

Apoptotic pathways and DNA synthesis are activated in neurons in the brains of individuals with Alzheimer disease (AD). However, the signaling mechanisms that mediate these events have not been defined. We show that expression of familial AD (FAD) mutants of the amyloid precursor protein (APP) in primary neurons in culture causes apoptosis and DNA synthesis. Both the apoptosis and the DNA synth...