Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We characterized anticancer effects of opioid analgesics that are clinically used for cancer patients for pain relief. Treatment with 100 microM buprenorphine, a representative analgesic, induced cell death of human carcinomas, such as A549 (squamous epithelial cell of lung cancer), MCF-7 (breast cancer) and N417 (small cell of lung cancer), but not in KATO III (gastric cancer) cells as evaluated by alamar blue assay. Among 18 clinically utilized and related analgesics, buprenorphine and loperamide showed potent inhibition of cell viability. However, these anti-cancer effects were not affected by opioid receptor antagonists nor by pertussis toxin. Buprenorphine-induced cell death occurred as early as 1 h after the addition, and its T1/2 of cell viability inhibition was 3 h. The cell death manifested the characteristics of apoptosis, such as DNA-laddering and nuclear fragmentation, which were sensitive to a caspase inhibitor, Z-Asp-CH2-DCB. The nuclear fragmentation was independent of cell cycle phase specificity. The activity of caspase-3-like protease which is known to be closely related to apoptotic DNA laddering was markedly enhanced by buprenorphine. However, the inhibition of cell viability by buprenorphine was not affected by the caspase inhibitor. These findings suggest that some opioid analgesics induce typical apoptotic features sensitive to the caspase inhibitor, while also inhibition of cell viability insensitive to the inhibitor.
 ...
PMID:Opioid analgesic-induced apoptosis and caspase-independent cell death in human lung carcinoma A549 cells. 1093 99

The skeleton is the most common site of metastatic disease in breast cancer and the most common site of first distant relapse. Bone metastases in breast cancer are the source of considerable morbidity, including severe pain, pathological fractures, need for radiotherapy or surgery, and hypercalcemia. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption, and it is well known that breast cancer cells in bone can stimulate osteoclast formation and activity leading to the release of growth factors and cytokines, which will further stimulate cancer cell growth and their secretion of osteolytic factors. We are thus typically dealing with a vicious cycle, as the bone resorption-induced release of growth factors from the bone matrix will stimulate breast cancer cell growth (probably mainly by IGFs) and the production of the osteolytic factor PTHrP (probably mainly by TGF-beta but also by extracellular calcium). Clodronate, but not the aminobisphosphonates, can be metabolized to an ATP analog that is toxic for osteoclasts. Nitrogen-containing bisphosphonates, such as pamidronate, ibandronate, and zoledronate, interfere with the mevalonate pathway that is crucial to maintain cell membrane integrity. The net result, regardless of the mechanism, is osteoclast apoptosis, notably through the induction of caspase-3. Bisphosphonates are now the standard treatment for cancer hypercalcemia. Repeated bisphosphonate infusions also exert clinically relevant analgesic effects in at least one half of the patients with metastatic bone pain. Most importantly, prolonged administration of bisphosphonates (for at least 1 year) reduces the frequency of morbid skeletal events by 30-40% in breast cancer metastatic to bone and in up to 50% in patients with multiple myeloma. Newer bisphosphonates, such as ibandronate and zoledronate, will simplify the current therapeutic schemes and improve the cost-effectiveness ratio, and they have the potential to improve the therapeutic efficacy, at least in patients with aggressive osteolytic disease or in the adjuvant setting.
 ...
PMID:Bisphosphonates in the treatment of metastatic breast cancer. 1201 36

Mistletoe extracts are used as alternative cancer treatment in addition to standard chemotherapy and radiation treatment and have an immunostimulatory and pain-relieving effect. A direct antitumour effect of mistletoe extracts against tumour cells of lymphoid origin has been linked to the D-galactoside-specific mistletoe lectin I. In this study, we investigated the cellular effect of bacterially expressed, recombinant mistletoe lectin alone or in combination with ionising radiation in a genetically defined p53-wild-type and p53-deficient E1A/ras-transformed murine tumour cells system. Downregulation of the proliferative activity and cell killing by recombinant mistletoe lectin occurred in a clear dose response (0.1-1 ng ml(-1)). Induction of apoptosis was p53-independent, but apoptosis-associated factor-1-dependent. Cellular treatment with lectin in combination with ionising radiation resulted in both p53-wild-type and p53-deficient tumour cells in an at least additive, antiproliferative effect and enhanced activation of caspase-3. Combined treatment with ionising radiation and lectin revealed a similar cytotoxic effect in human, p53-mutated adenocarcinoma cells. Thus, recombinant mistletoe lectin alone and in combination with ionising radiation bypasses often prevalent apoptotic deficiencies in treatment-resistant tumour cells.
 ...
PMID:Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation. 1277 96

Loose ligation of the rat sciatic nerve (chronic constriction injury (CCI) model) provokes signs and symptoms like those observed in complex regional pain syndrome (CRPS) patients. Neurogenic inflammation is a purported cause of neuropathic pain despite inconsistent evidence to support this hypothesis. To clarify this issue, we examined effects of CCI on microcirculation, inflammatory cell-cell interaction and cell integrity in muscle tissue using intravital fluorescence microscopic, molecular and immunohistochemical techniques. CCI-rats, but not sham-operated animals developed symptoms of neuropathic pain and oedema on the ipsilateral hindpaw. Despite signs of neuropathic pain, high resolution in vivo multifluorescence microscopy revealed physiological values for functional capillary density, leukocyte-endothelial cell interaction and microvascular permeability in muscle tissue of CCI-animals, similarly as found in controls, indicating absence of perfusion failure and inflammatory cell reaction. However, CCI-animals represented with marked apoptosis of bisbenzimide-stained muscle tissue cells, as given by in vivo fluorescence microscopic assessment of cell death-associated condensation, fragmentation and/or crescent-shaped formation of their nuclear chromatin. Apoptosis was further confirmed by increased caspase 3 protein levels and positive terminal deoxyuridine nick end labeling histochemistry. The present study demonstrates that sciatic nerve ligation-induced neuropathy causes cell apoptosis without concomitant inflammation-associated microcirculatory dysfunction in muscle tissue. Beside the well-known pattern of neuropathic pain, the CCI-model has now additionally been shown to reflect the response of muscle tissue to impaired innervation, i.e. prompting muscle cells to undergo non-inflammatory apoptotic cell death. This finding deserves further investigation in that apoptosis may contribute to neuropathic pain conditions like CRPS.
Pain 2004 Nov
PMID:In vivo evidence for apoptosis, but not inflammation in the hindlimb muscle of neuropathic rats. 1549 92

Bee venom (BV) has been used traditionally for the control of pain and inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA) in Oriental medicine. However, it is still unclear how BV exerts its beneficial effects on the clinical course of RA patients. To investigate the effect of BV on the treatment of rheumatoid synovitis, we examined the inhibition of cell growth and induction of apoptosis in human rheumatoid synovial fibroblasts. Rheumatoid synovial fibroblasts were surgically obtained from patients with RA. Cell proliferation and viability were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis of synovial cells treated with 10 microg/ml BV for 24 h was identified by 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, DNA fragmentation assay, RT-PCR, and Western blot analysis. It was demonstrated that rheumatoid synovial cells treated with 10 microg/ml BV for 24 h exhibited apoptotic features and fragmentation of DNA. In addition, BV induces apoptosis in rheumatoid synovial cells through a decrease in BCL2 expression and an increase in BAX and caspase-3 (CASP3) expression. It is suggested that BV inhibits the proliferation of rheumatoid synovial cells through induction of apoptosis by CASP3 activation.
 ...
PMID:Bee venom induces apoptosis through caspase-3 activation in synovial fibroblasts of patients with rheumatoid arthritis. 1592 90

It has been proposed that death of inhibitory interneurons in the dorsal horn contributes to the neuropathic pain that follows partial nerve injury. In this study, we have used two approaches to test whether there is neuronal death in the dorsal horn in the spared nerve injury (SNI) model. We performed a stereological analysis of the packing density of neurons in laminas I-III 4 weeks after operation and found no reduction on the ipsilateral side compared with that seen on the contralateral side or in sham-operated or naive rats. In addition, we used two markers of apoptosis, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining and immunocytochemical detection of cleaved (activated) caspase-3. Neither of these methods demonstrated apoptotic neurons in the dorsal spinal cord 1 week after operation. Although TUNEL-positive cells were present throughout the gray and white matter at this stage, they were virtually all labeled with antibody against ionized calcium-binding adapter molecule 1, a marker for microglia. All animals that underwent SNI showed clear signs of tactile allodynia affecting the ipsilateral hindpaw. These results suggest that a significant loss of neurons from the dorsal horn is not necessary for the development of tactile allodynia in the SNI model.
 ...
PMID:Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain. 1601 27

Soft tissue trauma induces an inflammatory response locally and in remote organs. Although remote organ failure is attributed to the systemic action of locally released mediators, it is so far unclear to what extent a direct cell injury and the consequences of ischemia or a secondary injury due to locally released mediators contribute to the manifestation of tissue damage at the primary site of trauma. Soft tissue trauma was induced by means of a controlled impact injury technique in the hind limb of pentobarbital-anesthetized rats. Additional animals received a femoral arterial infusion of supernatant of traumatized muscle tissue, of nontraumatized muscle, or 0.9% NaCl. Tissue injury was assessed by determining microcirculatory perfusion failure, inflammatory response, apoptotic cell death, and nociceptive pain behavior. Muscle tissue of traumatized animals revealed perfusion failure, tissue hypoxia, and inflammation. Nociceptive testing showed a decrease in mechanical pain thresholds of the affected hind paw. Infusion of supernatant of traumatized tissue induced local inflammation and pain comparable with that of directly traumatized tissue; however, it failed to cause nutritive perfusion failure. Supernatant of nontraumatized muscle did not affect muscle microcirculation and integrity. Only animals that underwent direct trauma presented with apoptotic cell death, as given by in vivo fluorescence microscopy, caspase 3 protein cleavage, and transferase-mediated dUTP nick-end labeling histology. Trauma-associated humoral factors cause post-traumatic hyperalgesia and inflammation, but not microvascular perfusion failure and apoptotic cell death. This finding may prompt future efforts in the therapy of closed soft tissue trauma to focus not only on antimediator strategies, but to add regimens targeting perfusion failure and tissue apoptosis.
 ...
PMID:Supernatant of traumatized muscle induces inflammation and pain, but not microcirculatory perfusion failure and apoptotic cell death. 1613 60

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used in the treatment of inflammation and pain. In many reports, NSAIDs have induced apoptosis in a variety of cell lines such as colon cancer cells. On the other hand, more recently a few reports have found that NSAIDs protect against apoptosis. Here we investigate endoplasmic reticulum (ER)-stress-induced apoptosis of neuronal cells. The aim of this study is to examine the involvement of NSAIDs, in particular diclofenac, on ER-stress-induced apoptosis of human neuroblastoma SH-SY5Y cells. Diclofenac significantly suppressed SH-SY5Y cell death induced by two types of ER-stress-inducing agents: thapsigargin, an inhibitor of Ca2+-ATPase on the endoplasmic reticulum membrane, and tunicamycin, a glycosylation blocker. Other NSAIDs, such as indomethacin, ibuprofen, aspirin, and ketoprofen, also suppressed ER-stress-induced SH-SY5Y cell death. The dose-dependent anti-apoptotic effect of diclofenac did not correlate with the reduction of prostaglandin release. Administration of prostaglandin E2, which was a primary product of arachidonic metabolism, showed no effects against anti-apoptotic effects produced by diclofenac. Thapsigargin and tunicamycin each significantly activated caspase-3, -9, and -2 in the intrinsic apoptotic pathway in SH-SY5Y cells. Diclofenac suppressed the activation of caspases induced by both ER stresses. Thapsigargin and tunicamycin decreased the mitochondrial membrane potential in SH-SY5Y cells. Diclofenac suppressed the mitochondrial depolarization induced by both ER stresses. Diclofenac inhibited ER-stress-induced apoptosis of SH-SY5Y cells by suppressing the activation of caspases in the intrinsic apoptotic pathway. This is the first report to find that diclofenac has protective effects against ER-stress-induced apoptosis.
 ...
PMID:Diclofenac, a non-steroidal anti-inflammatory drug, suppresses apoptosis induced by endoplasmic reticulum stresses by inhibiting caspase signaling. 1638 30

Prostate cancer is one of the most common non-skin cancers in men. Amygdalin is one of the nitrilosides, natural cyanide-containing substances abundant in the seeds of plants of the prunasin family that have been used to treat cancers and relieve pain. In particular, D-amygdalin (D-mandelonitrile-beta-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. Apoptosis, programmed cell death, is an important mechanism in cancer treatment. In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells. In the present results, DU145 and LNCaP cells treated with amygdalin exhibited several morphological characteristics of apoptosis. Treatment with amygdalin increased expression of Bax, a pro-apoptotic protein, decreased expression of Bcl-2, an anti-apoptotic protein, and increased caspase-3 enzyme activity in DU145 and LNCaP prostate cancer cells. Here, we have shown that amygdalin induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells by caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax. The present study reveals that amygdalin may offer a valuable option for the treatment of prostate cancers.
 ...
PMID:Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. 1688 Jun 11

A mouse model of neuropathic pain consisting of chronic constriction injury (CCI) of the sciatic nerve was used to examine the involvement of reactive oxygen species (ROS) in early spinal cord pro-apoptotic gene over-expression during the development of neuropathic pain. RT-PCR analysis showed increased expression of bax, apoptotic protease-activating factor-1 (apaf-1), and caspase-9 in the dorsal horn spinal cord 3 days after chronic constriction injury of sciatic nerve. Consistent with biomolecular data, a marked increase in TUNEL-positive and caspase-3 active form was observed by 3 days CCI. Administration of phenyl-N-tert-butylnitrone (PBN), a potent ROS scavenger, reduced the development of thermal hyperalgesia and mechanical allodynia at 1 and 3 days post-CCI, and decreased the mRNA levels of bax, apaf-1, and caspase-9. PBN also reduced apoptotic and active Caspase-3 positive profiles in the superficial laminae (I-III) of the spinal cord. This study provides evidence that PBN inhibits over-expression of pro-apoptotic genes and neural apoptosis in the spinal cord dorsal horn induced by early-CCI of the sciatic nerve. These findings suggest that ROS regulate expression of some apoptotic genes which might play a role in the onset of neuropathic pain.
 ...
PMID:Role of reactive oxygen species and spinal cord apoptotic genes in the development of neuropathic pain. 1720 36


1 2 3 4 5 6 7 8 9 10 Next >>