Glutathione regulates caspase-dependent ceramide production and curcumin-induced apoptosis in human leukemic cells.

Depletion of intracellular glutathione (GSH) is the prime hallmark of the progression of apoptosis. Previously, we reported that curcumin induces reactive oxygen species (ROS)-mediated depletion of GSH, which leads to caspase-dependent and independent apoptosis in mouse fibroblast cells (F. Thayyullathil et al.

Glutathione selectively inhibits Doxorubicin induced phosphorylation of p53Ser¹⁵, caspase dependent ceramide production and apoptosis in human leukemic cells.

Glutathione (GSH) is the most abundant non-protein antioxidant in mammalian cells. It has been implicated in playing an important role in different signal transduction pathways, and its depletion is an early hallmark in the progression of apoptosis in response to a number of proapoptotic stimuli. We have selectively investigated the role of GSH in cytotoxic response of Jurkat and Molt-4 human leukemic cells to the anti-cancer drug Doxorubicin.

Protein phosphatase 1-dependent dephosphorylation of Akt is the prime signaling event in sphingosine-induced apoptosis in Jurkat cells.

Sphingosine (SPH) is an important bioactive lipid involved in mediating a variety of cell functions including apoptosis. However, the signaling mechanism of SPH-induced apoptosis remains unclear. We have investigated whether SPH inhibits survival signaling in cells by inhibiting Akt kinase activity.

Purification and characterization of a second type of neutral ceramidase from rat brain: a second more hydrophobic form of rat brain ceramidase.

Ceramidases (CDase) are enzymes that catalyze the hydrolysis of N-acyl linkage of ceramide (Cer) to generate sphingosine and free fatty acids. In this study we report the purification and characterization of a novel second type of neutral ceramidase from rat brain (RBCDase II). Triton X-100 protein extract from rat brain membrane was purified sequentially using Q-Sepharose, HiLoad16/60 Superdex 200pg, heparin-Sepharose, phenyl-Sepharose HP, and Mono Q columns.

Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells.

Curcumin has been shown to induce apoptosis in various malignant cancer cell lines. One mechanism of curcumin-induced apoptosis is through the PI3K/Akt signaling pathway. Akt, also known as protein kinase B (PKB), is a member of the family of phosphatidylinositol 3-OH-kinase regulated Ser/Thr kinases.

UVC-induced apoptosis in Dubca cells is independent of JNK activation and p53(Ser-15) phosphorylation.

Ultraviolet C (UVC) irradiation in mammalian cell lines activates a complex signaling network that leads to apoptosis. By using Dubca cells as a model system, we report the presence of a UVC-induced apoptotic pathway that is independent of c-Jun N-terminal kinases (JNKs) activation and p53 phosphorylation at Ser(15). Irradiation of Dubca cells with UVC results in a rapid JNK activation and phosphorylation of its downstream target c-Jun, as well as, phosphorylation of activating transcription factor 2 (ATF2).

Akt depletion is an important determinant of L929 cell death following heat stress.

Exposure of mammalian cells to heat stress causes impairment of numerous physiological functions and activates a number of signaling pathways. Some of these pathways, such as induction of heat-shock proteins and activation of Akt, enhance the ability of cells to survive heat stress. On the other hand, heat stress can trigger cell-death signaling via activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/Jnk).

Investigation of heat stress response in the camel fibroblast cell line dubca.

We have used a camel cell line model (Dubca) to investigate the effect of heat stress on cell survival. The mechanism(s) of such survival response are very important not only for normal physiological function, but also, in pathological conditions, such as cancer. Those cells that have escaped the normal response to heat are an important model in helping us better understand the intricate signaling change(s) that might have occurred in changing a cell's phenotype from normal to cancerous.

Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells.

Evidence that curcumin may have anticancer activities has renewed interest in its potential to prevent and treat disease. In this study, we show that curcumin-mediated rapid generation of reactive oxygen species (ROS) leads to apoptosis by modulating different apoptotic pathways in mouse fibroblast L929 cells. We show for the first time that curcumin-induced rapid ROS generation causes the release of apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus, hence, leading to caspase 3-independent apoptosis.