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)

Epipremnum pinnatum (L.) Engl. hexane extract produced a significant growth inhibition against T-47D breast carcinoma cells and analysis of cell death mechanisms indicated that the extract elicited a non-apoptotic programmed cell death. T-47D cells exposed to the extract at EC(50) concentration (72 h) for 24 h failed to demonstrate typical DNA fragmentation associated with apoptosis, as carried out using a modified TUNEL assay. In addition, acute exposure to the extract produced an insignificant regulation of caspase-3 and p53 mRNA expression but increased in the c-myc mRNA expression. Ultrastructural analysis using transmission electron microscope demonstrated distinct vacuolated cells, which strongly indicated a Type II non-apoptotic cell death although the changes in chromatin were also detected. The presence of non-apoptotic programmed cell death was then reconfirmed with annexin-V and propidium iodide staining. These findings suggested that up-regulation of c-myc mRNA expression may have contributed to the growth arrest and Type II non-apoptotic programmed cell death in the Epipremnum pinnatum (L.) Engl. hexane extract-treated T-47D cells.
 ...
PMID:Growth arrest and non-apoptotic programmed cell death associated with the up-regulation of c-myc mRNA expression in T-47D breast tumor cells following exposure to Epipremnum pinnatum (L.) Engl. hexane extract. 1561 55

A hexane extract of the plant product Chios mastic gum (He-CMG) is demonstrated to kill human colon cancer cells in vitro via the process of anoikis. Specifically, the sequence of events includes He-CMG-induced GI-arrest of the cells, detachment of the cells from the substrate and subsequent apoptosis. Anoikis is dependent on the concentration and duration of treatment with He-CMG. Presence of the pan-caspase inhibitor, Z-VAD-fmk, did not prevent cell detachment, but it did prevent apoptosis of the detached cells indicating that the process of cell detachment, but not apoptosis, is independent of caspase activation. He-CMG-induced apoptosis is associated with activation of the initiator caspases-8, and -9 and the effector caspase-3. Caspases are activated in cells at a relatively long time after detachment, and caspase-3 activation may require caspase-8 or caspase-9 activation, as determined by using HCT116 isogenic clones impaired in apoptosis mechanisms that involve these two caspases. Finally, electron microscopy observations indicated a time-dependent appearance of morphological features both typical and non-typical of apoptosis in cells treated with He-CMG for various periods of time. Taken together, the results demonstrated that He-CMG induces apoptosis in HCT116 cells and, therefore, further in vivo and in vitro studies of the anticancer activities of this plant product are warranted.
 ...
PMID:Induction of apoptosis in human colon cancer HCT116 cells treated with an extract of the plant product, Chios mastic gum. 1579 60

Andrographolide was extracted and purified from Andrographis panicula using hexane and water partitioning followed by ethyl acetate extraction and chromatography. It showed selective cytotoxicity to prostate cancer PC-3 cells in vitro. The morphological and biochemical changes induced by the extract in carcinoma PC-3 cell death were studied. In andrographolide-treated cells, evidence of apoptosis such as cell shrinkage and surface microvilli loss after 4-hour treatment and chromatin condensation and fragmentation in H&E-stained cells between 4 to 8 hours after treatment were observed. Under electron microscopy, membrane blebbing and apoptotic bodies formation were seen after 8-hour treatment. Using immunocytochemistry staining and cellular caspase-3 activity assay, andrographolide-treated cells showed considerable caspase-3 activation and caspase-8 in PC-3 cells at 4 and 2 hours after treatment, respectively. This suggests andrographolide-induced cell death was achieved through the apoptotic pathway, via the activation of an extrinsic caspase cascade.
 ...
PMID:Morphological and biochemical changes of andrographolide-induced cell death in human prostatic adenocarcinoma PC-3 cells. 1587 75

Bcl-x exists in two isoforms, the anti-apoptotic form Bcl-xL and the proapoptotic form Bcl-xS. The critical balance between the two forms appears to be important for cell survival; however, it is still not clear exactly how the vital balance is maintained. Using an in vitro spermatogenic cell apoptosis model, this study provides a new insight into the possible role of Ca2+ in regulating the Bcl-xS and Bcl-xL expression. 2,5-Hexanedione, a metabolite of the common industrial solvent n-hexane, caused a significant increase in reactive oxygen species followed by an enhancement of intracellular Ca2+ through the T-type Ca2+ channels. Consequent to the above changes, expression of Bcl-xS increased with a concomitant drop in Bcl-xL expression, thus altering the ratio of the two proteins. Impediment of Ca2+ influx by using a T-type Ca2+ channel blocker pimozide resulted in a decrease in Bcl-xS and an increase in Bcl-xL expression. This caused prevention of mitochondrial potential loss, reduction of caspase-3 activity, inhibition of DNA fragmentation, and increase in cell survival. Alternatively, Ca2+ ionophores caused an increase of Bcl-xS encoding isoform over the Bcl-xL-encoding isoform. Therefore, this study proposes a role for Ca2+ in regulation of Bcl-xS and Bcl-xL expression and ultimately cell fate.
 ...
PMID:Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death. 1630 18

Astrocyte death may occur in neurodegenerative disorders and complicates the outcome of brain ischemia, a condition associated with high extracellular levels of adenosine and glutamate. We show that pharmacological activation of A(1) adenosine and mGlu3 metabotropic glutamate receptors with N(6)-chlorocyclopentyladenosine (CCPA) and (-)2-oxa-4-aminocyclo-[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), respectively, protects cultured astrocytes against apoptosis induced by a 3-h exposure to oxygen/glucose deprivation (OGD). Protection by CCPA and LY379268 was less than additive and was abrogated by receptor blockade with selective competitive antagonists or pertussis toxin. Both in control astrocytes and in astrocytes exposed to OGD, CCPA and LY379268 induced a rapid activation of the phosphatidylinositol-3-kinase (PI3K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2)/mitogen-activated protein kinase (MAPK) pathways, which are known to support cell survival. In cultures exposed to OGD, CCPA and LY379268 reduced the activation of c-Jun N-terminal kinase and p38/MAPK, reduced the levels of the proapoptotic protein Bad, increased the levels of the antiapoptotic protein Bcl-X(L), and were highly protective against apoptotic death, as shown by nuclear 4'-6-diamidino-2-phenylindole staining and measurements of caspase-3 activity. All of these effects were attenuated by treatment with 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126) and 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), which inhibit the MAPK and the PI3K pathways, respectively. These data suggest that pharmacological activation of A(1) and mGlu3 receptors protects astrocytes against hypoxic/ischemic damage by stimulating the PI3K and ERK1/2 MAPK pathways.
 ...
PMID:Molecular signalling mediating the protective effect of A1 adenosine and mGlu3 metabotropic glutamate receptor activation against apoptosis by oxygen/glucose deprivation in cultured astrocytes. 1729 59

Occupational exposure and experimental intoxication with n-hexane or its metabolite 2,5-hexanedione (HD) produce a central-peripheral neuropathy. However, the mechanism remains unknown. We hypothesized that HD affected the expression of Bcl-2, Bax and Caspase-3 in the central nervous system (CNS) and the peripheral nervous system (PNS). Male adult Wistar rats were administered by intraperitoneal injection at a dosage of 200 or 400 mg/kg HD, five days per week for 8 weeks. Samples of the cerebral cortex, cerebellum, spinal cord and sciatic nerves were collected and examined for Bcl-2, Bax and Caspase-3 expression using Western blotting. Subchronic exposure to HD resulted in significantly increased expression of both anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax and Caspase-3 in cerebral cortex and cerebellum, which exhibited a dose-dependent pattern. Though little change was detected in spinal cord, our results showed that the expression of Bcl-2, Bax and Caspase-3 was markedly enhanced in the sciatic nerves. These findings suggested that the changes of apoptosis-related protein level in rat nerve tissues were associated with the intoxication of HD, which might be involved in early molecular regulatory mechanism of apoptosis in the HD-induced neuropathy.
 ...
PMID:Expression of Bcl-2, Bax and Caspase-3 in nerve tissues of rats chronically exposed to 2,5-hexanedione. 1749 5

Uncaria tomentosa (Wild.) DC., found in the Amazon rain forest in South-America and known commonly as cat's claw, has been used in traditional medicine to prevent and treat inflammation and cancer. Recently, it has been found to possess potent anti-inflammation activities. In this study, we extracted cat's claw using four different solvents of different polarities and compared their relative influence on proliferation in human premyelocytic leukemia HL-60 cell lines. Cat's claw n-hexane extracts (CC-H), ethyl acetate extracts (CC-EA) and n-butanol extracts (CC-B) had a greater anti-cancer effect on HL-60 cells than those extracted with methanol (CC-M). Furthermore, CC-EA induced DNA fragmentation in HL-60 cells in a clearly more a concentration- and time-dependent manner than the other extracts. CC-EA-induced cell death was characterized by cell body shrinkage and chromatin condensation. Further investigating the molecular mechanism behind CC-EA-induced apoptosis, sells treated with CC-EA underwent a rapid loss of mitochondrial transmembrane (DeltaPsi(m)) potential, stimulation of phosphatidylserine flip-flop, release of mitochondrial cytochrome c into cytosol, induction of caspase-3 activity in a time-dependent manner, and induced the cleavage of DNA fragmentation factor (DFF-45) and PARP poly-(ADP-ribose) polymerase (PARP). CC-EA promoted the up-regulation of Fas before the processing and activation of procaspase-8 and cleavage of Bid. In addition, the apoptosis induced by CC-EA was accompanied by up-regulation of Bax, down-regulation of Bcl-X(L) and cleavage of Mcl-1, suggesting that CC-EA may have some compounds that have anti-cancer activities and that further studies using cat's claw extracts need to be pursued. Taken together, the results of our studies show clearly that CC-EA's induction of apoptosis in HL-60 cells may make it very important in the development of medicine that can trigger chemopreventive actions in the body.
 ...
PMID:Induction of apoptosis by Uncaria tomentosa through reactive oxygen species production, cytochrome c release, and caspases activation in human leukemia cells. 1761 71

Medullary thyroid carcinoma (MTC), a neuroendocrine tumor arising from the thyroid gland, is known to be poorly responsive to conventional chemotherapy. The root of Stemona tuberosa Lour, also called Bai Bu, is a commonly used traditional Chinese anti-tussive medicine. The present study investigated this medicinal herb for the first time with respect to its anticancer activity in human medullary thyroid carcinoma cells. Four extracts of Stemona tuberosa Lour, including the n-hexane fraction, (ST-1), dichloromethane (DCM) fraction, (ST-2), ethyl acetate (EtOAc) fraction, (ST-3), and methanol fraction, (ST-4) were examined for antiproliferative effects in two MTC cell lines. We observed that only the DCM fraction ST-2 inhibited cell growth and viability in a dose-dependent manner. Furthermore, we found that ST-2 also induced the apoptosis of MTC-SK cells. Caspase-3/7 was activated, while caspase-9 was not, implying that at least a caspase-dependent apoptotic pathway was involved in this process. In addition, the multicellular spheroids of MTC-SK were destroyed and the cell morphology was changed by ST-2. Our results show the strong apoptotic effects of the DCM fraction of Stemona tuberosa Lour on human medullary thyroid carcinomas, so suggesting a new candidate for chemotherapy of the so far chemo-resistant medullary thyroid carcinoma.
 ...
PMID:The dichloromethane fraction of Stemona tuberosa Lour inhibits tumor cell growth and induces apoptosis of human medullary thyroid carcinoma cells. 1970 15

Glycyrrhiza uralensis (licorice) is one of the most frequently prescribed ingredients in Oriental medicine, and licorice extract has been shown to exert anti-carcinogenic effects. However, its use as a cancer chemopreventive agent is rather limited, due to the fact that its principal component, glycyrrhizin, is known to induce hypertension. This study determined the effects of a hexane/ethanol extract of G. uralensis (HEGU), which contains undetectable amounts of glycyrrhizin, on the apoptosis of androgen-insensitive DU145 cells. HEGU induced apoptosis and increased the levels of cleaved caspase-9, caspase-7, caspase-3 and poly (ADP-ribose) polymerase (PARP). HEGU also induced mitochondrial membrane depolarization and cytochrome c release to the cytosol. HEGU increased the levels of Fas, death receptor 4 (DR4), cleaved caspase-8, Mcl-1S, and truncated Bid proteins. A caspase-8 inhibitor suppressed HEGU-induced apoptosis. An active fraction of HEGU was separated via column chromatography and the structure of the active compound isoangustone A was identified via 1H-NMR and 13C-NMR. Isoangustone A increased apoptotic cells, the cleavage of PARP and caspases, and the levels of DR4 and Mcl-1S. Transfection with DR4 small interfering RNA attenuated HEGU- and isoangustone A-induced apoptosis. These results demonstrate that the activation of DR4 contributes to HEGU- and isoangustone A-induced apoptosis of DU145 cells.
 ...
PMID:Isoangustone A present in hexane/ethanol extract of Glycyrrhiza uralensis induces apoptosis in DU145 human prostate cancer cells via the activation of DR4 and intrinsic apoptosis pathway. 2022 24

Inula racemosa Hook.f. commonly known as Pushkarmula (Compositae) has been used as a traditional drug in India, China and Europe. In the present study, 95% ethanolic extract of roots and its fractions (n-hexane, chloroform, n-butanol and aqueous) were evaluated for in vitro cytotoxicity against cancer cell lines of colon, ovary, prostate, lung, CNS and leukemia. The n-hexane fraction containing alantolactone and isoalantolactone as its major constituents was further studied for its mode of action in HL-60 cells. The lowest IC(50) value of n-hexane fraction was 10.25 microg/ml for Colo-205, a colon cancer cell line whereas, 17.86 microg/ml was the highest IC(50) value observed against CNS cancer cell line SF-295. Further studies on HL-60 cells treated with n-hexane fraction at 10, 25 and 50 microg/ml for 6h, revealed that it induces apoptosis through intrinsic as well as extrinsic pathways by generating reactive oxygen species (ROS) intermediates. Mitochondrial dysfunction prompted the release of cytochrome c, translocation of pro-apoptotic protein (Bax), activation of caspase cascade, resulting in the cleavage of some specific substrates for caspase-3 such as poly (ADP-ribose) polymerase (PARP), which eventually leads to apoptosis. The results of present study strongly support further research and development of bioactive constituents from Inula racemosa as potential anticancer agent with possible therapeutic implication.
 ...
PMID:Activation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inula racemosa. 2060 Aug 5


1 2 3 4 5 6 7 8 Next >>