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

Hydroxyketone chelators, deferiprone (HK1), maltol (HK3) and their related compounds (HK2, 4-8), were characterized for their cytotoxic profiles against oral human normal and tumor cells. Most hydroxyketones except HK6 showed relatively higher tumor-specific cytotoxicity. Deferiprone (HK1), which showed the highest tumor specificity, had 10 times higher cytotoxicity than maltol (HK3) in both human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma HSC-2 cell lines. The cytotoxic activity of HK1 against HL-60 and HSC-2 cells was reduced in the presence of FeCl3, while that of HK3 was significantly increased by FeCl3. Agarose gel electrophoresis showed that HK1 induced internucleosomal DNA fragmentation in HL-60 cells, but the addition of FeCl3 inhibited the DNA fragmentation. HK3 did not induce DNA fragmentation in HL-60 cells, regardless of the presence or absence of FeCl3. In HSC-2 cells, HK1 and 3 did not induce DNA fragmentation in the presence or absence of FeCl3. Colorimetric protease assay showed that HK1 activated the caspase 3, 8 and 9 in HL-60 cells. On the other hand, HK3 did not activate the caspase 3, 8 and 9 in HL-60 cells, but activated the caspase 3 only slightly in the presence of FeCl3. HK1 and 3 also activated the caspase 3, 8 and 9 in HSC-2 cells, but to a lesser extent. The present study suggested that the antitumor activity of hydroxyketones may be modified by Fe3+ concentration.
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PMID:Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines. 1516 Oct 23

In this study, we have evaluated the chemopreventive role of aloe-emodin in human promyelocytic leukemia HL-60 cells in vitro by studying the regulation of proliferation, cell cycle and apoptosis. Aloe-emodin inhibited cell proliferation and induced G2/M arrest and apoptosis in HL-60 cells. Investigation of the levels of cyclins B1, E and A by immunoblot analysis showed that cyclin E level was unaffected, whereas cyclin B1 and A levels increased with aloe-emodin in HL-60 cells. Investigation of the levels of cyclin-dependent kinases, Cdk1 and 2, showed increased levels of Cdk1 but the levels of Cdk2 were not effected with aloe-emodin in HL-60 cells. The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 microM aloe-emodin for 12, 24, 48, and 72 hours. Taken together, aloe-emodin therefore appears to exert its anticarcinogenesis properties by inhibiting proliferation and inducing cell cycle arrest and apoptosis underwent activation of caspase-3 in human leukemia HL-60 cells.
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PMID:Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells. 1520 75

Echinocystic acid (EA) is a natural triterpone enriched in various herbs and used for medicinal purpose in many Asian countries. In the present study, we reported that EA can induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation, poly (ADP) ribose polymerase cleavage. The efficacious induction of apoptosis was observed at 100 microM for 6 h. Further molecular analysis showed that EA induced the cleavage of Bid protein, the loss of mitochondrial membrane potential (DeltaPsim) cytochrome c release from mitochondria into cytosol, and activation of caspase-3, -8 and -9. However, EA did not generate reactive oxygen species (ROS), and antioxidants including N-acetyl cysteine and catalase could not block EA-induced apoptosis in the HL-60 cells. These data suggest that EA induces apoptosis in HL-60 cells through ROS-independent mitochondrial dysfunction pathway.
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PMID:Echinocystic acid induces apoptosis in HL-60 cells through mitochondria-mediated death pathway. 1524 58

Gossypol is a component present in cottonseeds and has been demonstrated to be an effective contraceptive drug in preventing spermatogenesis in mammalian species. In the present, we reported that gossypol could induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation, poly(ADP) ribose polymerase (PARP) cleavage. The efficacious induction of apoptosis was observed at 50 microM for 6 h. Further molecular analysis showed that gossypol induced the truncation of Bid protein, the loss of mitochondrial membrane potential (DeltaPsi m), cytochrome c release from mitochondria into cytosol, and activation of caspase-3, -8, and -9. However, gossypol did not increase the level of reactive oxygen species (ROS), and antioxidants including N-acetyl cysteine (NAC) and catalase could not block gossypol-induced apoptosis in the HL-60 cells. These data suggest that gossypol induces apoptosis in HL-60 cells through ROS-independent mitochondrial dysfunction pathway.
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PMID:Involvement of reactive oxygen species-independent mitochondrial pathway in gossypol-induced apoptosis. 1524 75

Yomogin is an active compound isolated from Artemisia princep, a traditional Oriental medicinal herb, which has been shown to inhibit tumor cell proliferation. In this study, we investigated the effects of yomogin on the cytotoxicity, induction of apoptosis, and putative pathways of its actions in human promyelocytic leukemia cells. Yomogin-treated HL-60 cells displayed several features of apoptosis, including DNA fragmentation, formation of DNA ladders in agarose gel electrophoresis, and externalization of annexin-V targeted phosphatidylserine residues. We observed that yomogin caused activation of caspase-8, caspase-9, and caspase-3. A general caspase inhibitor (z-VAD-fmk), caspase-8 inhibitor (z-IETD-fmk) and caspase-3 inhibitor (z-DEVD-fmk), almost completely suppressed the yomogin-induced DNA fragmentation. We further demonstrated that yomogin induced Bid cleavage, mitochondrial translocation of Bax from the cytosol, and cytochrome c release from mitochondria in a caspase-8-dependent manner. Taken together, our data indicate that yomogin is a potent inducer of apoptosis and facilitates its activity via caspase-8 activation, Bid cleavage, Bax translocation to mitochondria, and subsequent release of cytochrome c into the cytoplasm, providing a potential mechanism for the anticancer activity of yomogin.
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PMID:Induction of apoptosis by yomogin in human promyelocytic leukemic HL-60 cells. 1525 49

These studies explore the molecular effect of arsenicals on MM cells. Freshly isolated cells derived from patients with advanced, chemo-refractory myeloma as well as human myeloma cell lines, ARP-1, RPMI-8226 and H929 were exposed to the organic arsenical melarsoprol and to the inorganic compound AT. Both agents potently induced apoptosis in myeloma cells. Exposure to 1-5 microM AT or melarsoprol for 6 hours suppressed NF-kappa B DNA binding and enhanced of c-Jun kinase (JNK) activity. Arsenic also activated caspase-3 resulting in the cleavage of poly (ADP-ribose) polymerase (PARP) and Fas/TNF alpha related receptor interacting protein (RIP). In contrast to reported observations in acute promyelocytic leukemia, myeloma cell apoptosis was not associated with either the downregulation of Bcl-2 protein or with alterations in the expression of other Bcl-2 family members, Bax, Bak, Bag, and Bcl-xl. This study first shows that arsenic induces apoptotic signaling in MM through the cleavage of TNF alpha related receptor interacting protein (RIP). RIP is a key downstream protein in FasL/ TNF alpha /TRAIL induced apoptosis and a major antiapoptotic adaptor of pathways through NF-kappa B and JNK. RIP has not been previously characterized in myeloma. This study supports the hypothesis that arsenicals share common mediators (RIP, NF-kappa B, PARP, caspase-3) with death receptor induced apoptosis. These studies provide an important insight into the molecular mechanism of AT induced apoptosis and can be used in the development of adjuvant therapy for MM, presently an incurable disease.
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PMID:RIP kinase is involved in arsenic-induced apoptosis in multiple myeloma cells. 1531 84

The crude extract of Ampelopsis cantoniensis induced apoptosis in human promyelocytic leukemia HL-60 cells and this induction was investigated by flow cytometric analysis, DNA gel electrophoresis and poly (ADP-ribose) fluorescence staining. The results demonstrated that this extract induced dose-dependent cytotoxicity and apoptosis. The level of active caspase-3 was increased after treatment with the crude extract for 24 hours.
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PMID:Induction of apoptosis in human promyelocytic leukemia HL-60 cells by Ampelopsis cantoniensis crude extract. 1536 84

Baicalein is one component of the dried root of Scutellaria Baicalensis Georgi. (Huang Qin) which is widely used in the traditional Chinese herbal medicine. In this study, we report that baicalein was able to induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by poly-(ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation. The efficacious induction of apoptosis was observed at 100 microM for 6 h. Mechanistic analysis demonstrated that baicalein induced the cleavage of Bid protein, cytochrome c release from mitochondria into cytosol, and activation of caspase-3, -8 and -9. Moreover, baicalein caused elevation of intracellular hydrogen peroxide level. Catalase could effectively block baicalein-induced DNA fragmentation. These data indicate that baicalein may trigger an apoptotic death program through reactive oxygen species (ROS)-mediated mitochondrial dysfunction pathway. The findings enhance our understanding of anticancer function of baicalein in herbal medicine.
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PMID:Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells. 1537 93

Two relatively recent discoveries stand behind our current effort to investigate the effects of the chemopreventive agent, selenium, on the proliferation and survival of NB4 cells. The first is that certain selenium compounds such as sodium selenite have pro-oxidant ability to catalyze the oxidation of thiols and simultaneously generate superoxide. The second lies in the exquisite susceptibility of NB4 cells to arsenic trioxide-induced, reactive oxygen species (ROS)-mediated apoptosis due to less efficiency of the cellular defense system. In this study, we demonstrated that sodium selenite could induce apoptosis in NB4 cells via the classic mitochondrial pathway involving caspase-3 activation and Bcl-2 cleavage. An increase in the basal cellular glutathione (GSH) content rendered NB4 cells resistant to arsenic trioxide, but could sensitize NB4 cells to sodium selenite. Moreover, combined treatment of NB4 cells with all- trans retinoic acid (ATRA) at low concentration and sodium selenite exhibited a synergistic effect on apoptosis induction. Together, our results suggest that selenite is a promising candidate for treatment of acute promyelocytic leukemia (APL) and the mechanism underlying its anticancer effects warrants further investigation.
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PMID:Sodium selenite induces apoptosis in acute promyelocytic leukemia-derived NB4 cells by a caspase-3-dependent mechanism and a redox pathway different from that of arsenic trioxide. 1548 Jun 64

Arsenic trioxide is valuable for treatment of promyelocytic leukemia, but less attention has been paid to its therapeutic potential for other cancers. In this study, the effects of arsenic trioxide were tested in human pancreatic (AsPC-1), colonic (HT-29), and breast (MCF-7) cancer cells. In all three cancer cell lines, arsenic trioxide inhibited proliferation in a concentration and time-dependent manner, as measured by 3H-methyl thymidine incorporation and cell counting. Coincident with inhibition of growth, arsenic trioxide induced marked morphologic changes, including reduced cytoplasmic volume, membrane blebbing, and nuclear condensation consistent with apoptosis. Propidium iodide DNA staining at 24 hours revealed cell cycle arrest in the G0/G1 phase and an increase in the S phase, while at 72 hr there was G2/M phase arrest with a marked increase in the sub-G0/G1, apoptotic cell population. The DNA fragmentation induced by arsenic trioxide was confirmed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay in all cell lines. Western blot analysis revealed activation of caspase -3, -7, and -9 by arsenic trioxide. Caspase-3 activity was confirmed by demonstrating cleavage of its downstream target, poly ADP-ribose polymerase (PARP). Expression of the antiapoptosis protein, Bcl-2, was time-dependently decreased. In contrast, arsenic trioxide markedly enhanced the expression of the p21 protein, GADD45 and GADD153, in a time-dependent manner. These findings suggest that arsenic trioxide has potential as a therapeutic agent for these cancers.
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PMID:Arsenic trioxide causes redistribution of cell cycle, caspase activation, and GADD expression in human colonic, breast, and pancreatic cancer cells. 1549 60


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