As a form of new programmed cell death, pyroptosis is divided into a canonical pyroptosis pathway and a non-canonical pyroptosis pathway. In recent years, it is reported that non-canonical pyroptosis is closely related to inflammatory reactions, which directly affects the occurrence, development, and outcome of sepsis, inflammatory bowel disease, respiratory disease, nerve system inflammatory disease, and other inflammatory diseases. When the cells were infected with Gram-negative bacteria or lipopolysaccharide (LPS), it can induce the activation of cysteinyl aspartate specific proteinase(caspase)-4/5/11 and directly bind to the cells to cleave gasdermin D (GSDM-D) into the active amino-terminus of GSDM-D. The amino-terminus of GSDM-D with membrane punching activity migrates to the cell membrane, triggering the rupture of the cell membrane, and the cell contents discharge, leading to the occurrence of non-canonical pyroptosis. After activation of caspase-11, it also promotes the canonical pyroptosis, activates and releases interleukin-1β and interleukin-18, which aggravated inflammation. Caspase-4/5/11, GSDM-D, Toll-like receptor 4 and high mobility group protein B1 are the key molecules of the non-canonical pyroptosis. Exploring the mechanisms of non-canonical pyroptosis and the related research progresses in inflammatory diseases intensively is of great significance for clinical prevention and treatment of the relevant diseases.
Caspases ; Humans ; Inflammasomes ; Inflammation ; Lipopolysaccharides ; Pyroptosis ; Sepsis

Epilepsy is one of the most common episodic neurological diseases characterized by recurrent epileptic seizures. The seizures occur by synchronization of a neuronal network, which may cause disturbances in intracellular ion homeostasis, neuronal excitability, network remodeling, and neuronal death. The neuronal death following epileptic seizures results from the execution of cellular programs that are similar to those in developmentally programmed cell death. Research into cell death after seizures has identified the molecular machinery of apoptosis including the caspases and bcl-2 family proteins. The author reviews the clinical experimental evidences of programmed death pathway function in epileptic seizures. Four neuronal death pathways after epileptic seizures are proposed; non-programmed necrotic, programmed necrotic, programmed apoptotic extrinsic, and programmed apoptotic intrinsic pathways. Epileptogenesis is speculated based on the programmed pathways. Research on seizure-induced neuronal damage has developed considerably in recent years and that may open new ways to improve neuroprotective and antiepileptic treatments for patients with epilepsy.
Apoptosis ; Caspases ; Cell Death* ; Epilepsy* ; Homeostasis ; Humans ; Neurons ; Seizures

Caspases ; genetics ; Genetic Predisposition to Disease ; Humans ; Neoplasms ; genetics ; Polymorphism, Genetic

Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC₅₀ value of 3.49 μmol·L^-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.
Apoptosis ; Bone Neoplasms ; Caspases ; Humans ; Osteosarcoma/drug therapy* ; Penicillium

Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent and - independent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.
Animals ; Apoptosis ; physiology ; Caspases ; metabolism ; Caspases, Effector ; metabolism ; Cyclic GMP ; metabolism ; Mitochondria ; metabolism ; physiology ; Nitric Oxide ; metabolism ; physiology ; Plant Cells ; Plant Physiological Phenomena ; Signal Transduction ; physiology

alpha-Curcumene is one of the physiologically active components of Curcuma zedoaria, which is believed to perform anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the mechanism of the apoptotic effect of alpha-curcumene on the growth of human overian cancer, SiHa cells. Upon treatment with alpha-curcumene, cell viability of SiHa cells was inhibited > 73% for 48 h incubation. alpha-Curcumene treatment showed a characteristic nucleosomal DNA fragmentation pattern and the percentage of sub-diploid cells was increased in a concentration-dependent manner, hallmark features of apoptosis. Mitochondrial cytochrome c activation and an in vitro caspase-3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of alpha-curcumene, which mediates cell death. These results suggest that the apoptotic effect of alpha-curcumene on SiHa cells may converge caspase-3 activation through the release of mitochondrial cytochrome c.
Apoptosis ; Caspase 3 ; Caspases ; Cell Death ; Cell Survival ; Curcuma* ; Cytochromes c ; DNA Fragmentation ; Humans ; Ovarian Neoplasms*

Epilepsy is one of the most common episodic neurological diseases, and patients with epilepsy may experience a range of neurological, psychological, and behavioral problems. Recurring seizures potentially contribute to the progressive severity of epilepsy, cognitive and behavioral consequences. The clinical and experimental evidences involving radiological, pathological, and biochemical studies suggest that seizures can potentially injure the brain via a number of diverse molecular, cellular, and network mechanisms. The damage includes neuronal death, axodendritic changes, molecular changes of synaptic membrane, and gliosis and increased neurogenesis. Those changes induce rewiring of the network and reorganization of synapses, causing alteration of the functional and morphological properties as the mechanism of epilepsy. As the most overt form of alterations, the neuronal death may result from the execution of cellular programs that are similar to the molecular machinery of programmed cell death including the caspases and bcl-2 family proteins. In epileptic seizure, the neurons are overexcited and run out of energy. The low energy state is closely related with the necrotic pathway. The features suggest that the neuronal death in epilepsy may follow characteristic mechanism, suggesting necrotic programmed cell death pathway. Therapeutic modification of seizure-induced death could open new strategy in epilepsy treatment.
Brain ; Caspases ; Cell Death ; Epilepsy* ; Gliosis ; Humans ; Neurogenesis ; Neurons* ; Seizures ; Synapses ; Synaptic Membranes

PURPOSE: The potential therapeutic application of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in the treatment of multiple myeloma (MM), was recently proposed. However, there have been some problems with the use of TRAIL, due to the appearance of TRAIL-resistant cells in MM. The effect of arsenic trioxide (As2O3) on the rate of apoptosis induced by TRAIL was evaluated in MM cells. MATERIALS AND METHODS: Using TRAIL-sensitive (RPMI- 8226) and TRAIL-resistant (ARH-77 and IM-9) MM cell lines, the cell viability, induction of apoptosis, and change in the caspases were examined after treatment with TRAIL alone, or in combination with various concentrations of As2O3. RESULTS: Incubating the cell lines with As2O3 augmented the TRAIL-induced apoptosis in the MM cell lines, according to the As2O3 concentration. Apoptosis was mediated through caspase activation. When TRAIL was used alone, caspase8 was activated in the RPMI-8226 cell lines, but not in the ARH-77 and IM-9 cell lines. When As2O3 was added to TRAIL, caspase-9 was activated in the ARH-77 and IM-9 cells. CONCLUSION: The use of As2O3, in combination with TRAIL, would help enhance the level of TRAIL-induced apoptosis, and overcome the TRAIL-resistance, in MM cells.
Apoptosis* ; Arsenic* ; Caspase 9 ; Caspases ; Cell Line* ; Cell Survival ; Multiple Myeloma* ; Necrosis*

OBJECTIVE: To determine whether oxidants are formed as part of the cisplatin-induced apoptotic process, intracellular markers of oxidative stress were examined. METHODS: Apoptotic death of HeLa cells by cisplatin was confirmed by flow cytometry. RESULTS: The pre-treatment with glutathione (GSH) significantly attenuated cisplatin-induced apoptosis through the reduction of reactive oxygen species (ROS) accumulation and diminished caspases-3 and 9 protease activity. Furthermore, z-VAD-fmk, an inhibitor of pan-caspase, effectively inhibited the activation of caspases and prevented apoptosis by cisplatin, although cisplatin-induced ROS generation was not attenuated. CONCLUSION: These data indicate that ROS may play a role as an upstream mediator of caspases. Taken together, our results suggest that oxidative stress mediates cisplatin-induced apoptosis in HeLa cells.
Apoptosis* ; Caspases ; Cisplatin ; Flow Cytometry ; Glutathione ; HeLa Cells* ; Humans ; Oxidants ; Oxidative Stress* ; Reactive Oxygen Species

BACKGROUND: Human telomerase is a ribonucleoprotein polymerase, which synthesizes telomeric repeat sequences, and human telomerase reverse transcriptase (hTERT) has been identified as the catalytic subunit, as well as the rate-limiting component, of telomerase. In this study, we attempted to identify the modulators of telomerase, and to determine the molecular mechanisms underlying cisplatin-induced apoptosis. METHODS: To determine the role of telomerase in cisplatin-induced apoptosis, we measured telomerase activity and analyzed apoptosis using PI and trypan blue staining. Also, we inhibited the caspase activations using Z-VAD-fmk to analyze the effects on expression of hTERT protein. Finally, we induced the transient co-expression of the Bcl-2 and Bak genes in HEK293 cells, and then, the telomerase activity and expression of hTERT were evaluated. RESULTS: In the Bcl-2-overexpressing HeLa cells, telomerase activity was more enhanced, and cell death was reduced to 40-50% that of the mock controls. This finding suggests that Bcl-2-induced telomerase activity exerts an antiapoptotic effect in cisplatin-induced death. As caspase activation was inhibited via Z-VAD-fmk, the hTERT protein was recovered in the mock controls, but not in the Bcl-2-overexpressing cells. This suggests that the expression of hTERT can be regulated by caspases, but Bcl-2 was located within the upstream pathway. Moreover, when the Bcl-2 and Bak genes were co-transfected into the HEK293, both telomerase activity and hTERT protein were prominently reduced. CONCLUSIONS: Bcl-2-induced telomerase activity inhibits cisplatin-induced apoptosis in HeLa cells, and can be regulated via both caspases and the interaction of Bcl-2 and Bak.
Apoptosis ; Caspases* ; Catalytic Domain ; Cell Death* ; Cisplatin ; HEK293 Cells ; HeLa Cells ; Humans* ; Ribonucleoproteins ; Telomerase* ; Trypan Blue