Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antrodia camphorata (A. camphorata) is well known in Taiwan as a traditional Chinese medicine, and it has been shown to exhibit antioxidant effects. In this study, the ability of A. camphorata to induce apoptosis was studied in cultured human premyelocytic leukemia HL-60 cells. Treatment of the HL-60 cells with a variety of concentrations of the fermented culture broth of A. camphorata (25-150 microg/ml) resulted in dose- and time-dependent sequences of events marked by apoptosis, as shown by loss of cell viability, chromatin condensation, and internucleosomal DNA fragmentation. Furthermore, apoptosis in the HL-60 cells was accompanied by the release of cytochrome c, activation of caspase-3, and specific proteolytic cleavage of poly (ADP-ribose) polymerase (PARP). This increase in A. camphorata-induced apoptosis was also associated with a reduction in the levels of Bcl-2, a potent cell-death inhibitor, and an increase in those of the Bax protein, which heterodimerizes with and thereby inhibits Bcl-2. The data suggest that A. camphorata exerts antiproliferative action and growth inhibition on HL-60 cells through apoptosis induction and that it may have anticancer properties valuable for application in drug products.
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PMID:Induction of apoptosis by Antrodia camphorata in human premyelocytic leukemia HL-60 cells. 1523 54

It has been shown that humic acid (HA), a phenolic polymer, exhibits pro-oxidant and cytotoxic effects. In this study, HA induction of apoptosis was studied using cultured human premyelocytic leukemia HL-60 cells. Treatment at a range of HA concentrations (50-400 microg/ml) resulted in dose-and time-dependent sequences of events marked by apoptosis, as demonstrated through by apoptotic features such as loss of cell viability, chromatin condensation, and internucleosomal DNA fragmentation. This HA-induced apoptosis in the HL-60 cells was mainly associated with the release of cytochrome c from the mitochondria. Furthermore, apoptosis in the HL-60 cells was accompanied by the activation of caspase-3 and the specific proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), a major component in the apoptotic cell death mechanism. Although the HA-induced apoptosis was associated with Bax protein levels, negligible Bcl-2 reduction was observed. Analysis of the data reported herein reveals that HA exerts antiproliferative action and growth inhibition on HL-60 cells through induction of apoptosis, which may have anticancer properties potentially useful for the development of new drug products.
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PMID:Humic acid induces apoptosis in human premyelocytic leukemia HL-60 cells. 1530 26

Spatholobi Caulis has been used in Oriental medicine to treat cancer and blood stasis. In this study, the methylene chloride fraction of Spatholobi Caulis (MCSC) was examined to determine if it possesses anti-cancer activity via its apoptosis-inducing activity. MCSC exhibited a strong cytotoxic effect against human monocyte leukemia U937 cells (IC(50)=15.1 microg/ml). A TUNEL assay showed that the MCSC caused a characteristic ladder pattern of discontinuous DNA fragments and apoptotic bodies. Flow cytometric analysis confirmed that MCSC significantly increases the number of apoptotic cells stained by annexin V(+)/PI(-) cells. Western blotting revealed that MCSC activated caspase-3 expression and cleaved poly (ADP-ribose) polymerase (PARP) in a concentration-dependent manner. An enzyme-linked immunosorbent assay (ELISA) demonstrated that MCSC significantly activated the caspase-3 activity compared with the untreated control by. Taken together, these results suggest that MCSC can induce apoptosis in U937cells via the caspase dependent pathway.
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PMID:Methylene chloride fraction of Spatholobi Caulis induces apoptosis via caspase dependent pathway in U937 cells. 1534 Feb 17

This study examined the cytotoxicity of Scytosiphon lomentaria, using various cancer cell lines. The ethyl acetate (EtOAc) fraction of this alga showed the cytotoxicity to leukemia cells, including HL-60. When HL-60 cells were treated with its EtOAc fraction, several apoptotic characteristics, such as DNA fragmentation, chromatin condensation, and an increase of the population of sub-G1 hypodiploid cells, were observed. Moreover, the EtOAc fraction decreased c-Myc expression in a dose-dependent manner. In order to understand the mechanism of apoptosis induction by S. lomentaria, we examined the changes of Bcl-2 and Bax protein expression levels. The EtOAc fraction reduced Bcl-2, an antiapoptotic protein, but increased Bax, a proapoptotic protein, in a dose-dependent manner. When we examined the activation of caspase-3, an effector of apoptosis, the expression of the active form (19 kDa) of caspase-3 increased, and the increase of their activities was demonstrated by the cleavage of poly (ADP-ribose) polymerase, a substrate of caspase-3, to 85 kDa. The results suggest that the inhibitory effect of S. lomentaria on the growth of HL-60 appears to arise from the induction of apoptosis by way of the down-regulation of Bcl-2 and the activation of caspase.
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PMID:The cytotoxicity of Scytosiphon lomentaria against HL-60 promyelocytic leukemia cells. 1565 Apr 57

Eicosapentaenoic acid (EPA) induced apoptosis of rat basophilic leukemia cells (RBL2H3 cells), whereas 100 microM linoleic acid (LA) had no significant effect. Cytochrome c was released at 4 h. Apoptosis was detected at 6 h after exposure to EPA and docosahexaenoic acid (DHA), and preceded the activation of caspase-3. Liberation of apoptosis-inducing factor (AIF) from mitochondria and its translocation into the nucleus were observed at 4 h. A broad-specificity caspase inhibitor, z-VAD-fmk, failed to suppress the apoptosis, suggesting that EPA induced caspase-independent apoptosis. On other hand, a poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor that blocks AIF translocation to the nucleus suppressed EPA-induced apoptosis. The level of hydroperoxide in the cells and mitochondria increased at the early phase of apoptosis within 2 h. On the contrary, elevation of hydroperoxide in mitochondria was not observed after treatment with LA. The EPA-induced apoptosis was abolished by prevention of the hydroperoxide elevation in mitochondria via overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx). Neither cytochrome c nor AIF were released from mitochondria in the mitochondrial PHGPx-overexpressing cells. EPA also induced apoptosis in HeLa cells, but not in L929 or RAW264.7 cells. Enhancement of the hydroperoxide level in mitochondria was found in the EPA-sensitive HeLa cells after treatment with EPA, whereas no such enhancement was observed in the apoptosis-resistant L929 and RAW264.7 cells. These results suggest that the generation of hydroperoxide in mitochondria induced by EPA is associated with AIF release from mitochondria and the induction of apoptosis.
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PMID:Involvement of hydroperoxide in mitochondria in the induction of apoptosis by the eicosapentaenoic acid. 1578 27

The transition metal zinc (Zn) is an endogenous regulator of apoptosis. The ability of Zn to modulate apoptosis is believed to be mediated by the regulation of caspase activity. Previously, we reported that an acute influx of labile Zn induced apoptosis via activation of caspase in human leukemia HL-60 cells treated with a Zn ionophore (Py, pyrithione) and Zn at 1 and 25 microM, respectively. In the present study, we investigated the involvement of caspase-3 in Py (1 microM)/Zn (25 microM)-induced apoptosis in HL-60 cells. Pro-caspase-3 is an inactive form of caspase-3. The processing of pro-caspase-3, a sign of caspase-3 activation, occurred 6 h after treatment with Py/Zn. Proteolysis of poly (ADP-ribose) polymerase (PARP), a substrate of caspase-3, was also observed 6 h after treatment with Py/Zn. We also confirmed the elevation of caspase-3 activity as an index of the cleavage of amino acid sequences recognized by activated caspase-3. An inhibitor of caspase-3 attenuated the appearance of the DNA ladder. Taken together, these results indicate that the activation of caspase-3 is partly responsible for the induction of apoptosis in Py/Zn-treated HL-60 cells.
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PMID:Activation of caspase-3 in HL-60 cells treated with pyrithione and zinc. 1580 26

The response of three human leukemia cell lines, the proliferative promonocyte THP-1 and the promyeloid HL60 cells and the non-proliferative phorbol ester-treated HL60 cells (HL60/PMA), to oxidative stress induced by tert-butylhydroperoxide (t-BHP) treatment was analyzed by fluorescence microplate assay, anti-oxidant enzyme activity measurements, high performance liquid chromatography, yopro-1/PI incorporation, poly (ADP-ribose) polymerase and caspase 3 cleavages. After t-BHP treatment, the non-proliferative HL60/PMA cells exhibited a weak increase in reactive oxygen species (ROS) production, a better preservation of thiol content, a decrease of glutathione peroxidase activity and a high ability to undergo necrosis rather than apoptosis. Submitted to the same treatment, the proliferative HL60 and THP-1 cells exhibited a high increase of ROS production, a moderate thiol depletion and a high percentage of apoptosis. Under thiol depleting conditions, the oxidative treatment of the HL60/PMA cells resulted in a high ROS production that reached levels similar to those of the two other cell lines and in cell death mainly by necrosis. In conclusion, these results that show proliferative phenotype is essential for cell response towards oxidative stress, are of particular interest in chemotherapy involving an oxidative mechanism.
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PMID:Differential responses of proliferative and non-proliferative leukemia cells to oxidative stress. 1587 6

1. Cardiotoxin (CTX) III is a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom. This is the first report on the mechanism of the anticancer effect of CTX III on human leukaemia K562 cells. 2. Cardiotoxin III was found to inhibit the growth of K562 cells in a time- and dose-dependent manner, with an IC(50) value of 1.7 mug/mL, and displayed several features of apoptosis, including apoptotic body formation, an increase in the sub-G(1) population, DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage. 3. Investigation of the mechanism of CTX III-induced apoptosis revealed that treatment of K562 cells with CTX III resulted in the loss of mitochondrial membrane potential, cytochrome c release from mitochondria into the cytosol and activation of caspase-9 and caspase-3 and the subsequent cleavage of the caspase-3 substrate PARP; however, CTX III did not generate reactive oxygen species (ROS). 4. Taken together, the results indicate that CTX III induces apoptosis in K562 cells through an ROS-independent mitochondrial dysfunction pathway.
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PMID:Cardiotoxin III induces apoptosis in K562 cells through a mitochondrial-mediated pathway. 1602 8

The Tibetan herbal remedy PADMA 28 revealed promising results to support treatment of atherosclerosis, Charot syndrome (intermittent claudication), chronic active hepatitis and infection of the respiratory tract. The remedy was confirmed to be closely linked with anti- and pro-oxidative properties in vitro. In this study, apoptogenic and survival effects of PADMA 28 were investigated in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. PADMA 28 led to a concentration-dependent inhibition of cell proliferation accompanied by the accumulation of CEM-C7H2 cells in subG1 phase, fragmentation of poly (ADP-ribose) polymerase (PARP) and nuclear body formation. Treatment with PADMA 28 rescued to some extent cells over-expressing Bcl-2 from apoptosis. This finding suggests that the mechanism of action of PADMA 28 may be via interference with Bcl-2 triggered survival pathways.
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PMID:Apoptosis induced by the Tibetan herbal remedy PADMA 28 in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. 1613 18

Trichosanthis kirilowii MAXIM has been used as a folk remedy to treat diabetes, leukemia, and breast cancer. In the present study, the apoptotic mechanism of the methylene chloride fraction of Trichosanthis Fructus (MCTF) was investigated in human leukemic U937 cells. MCTF exhibited antiproliferative effectsagainst U937 cells (IC50=ca. 8 microg/ml). Apoptotic bodies were observed in MCTF-treated U937 cells in the TUNEL assay. We also confirmed that MCTF significantly increases annexin V(+)/propidium iodide-cells using FACS analysis. MCTF treatment activated caspase-8, -9 and -3, and led to cleaved poly (ADP-ribose) polymerase and release of cytochrome c into cytosol in a concentration-dependent manner, while MCTF did not affect Bax or Bcl-2 protein levels as shown by Western blot analysis. Taken together, these results indicate that MCTF can induce apoptosis in U937 cells chiefly via a mitochondrial-mediated pathway and suggest that Trichosanthis Fructus can be used in cancer treatment as a chemopreventive agent.
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PMID:The methylene chloride fraction of Trichosanthis Fructus induces apoptosis in U937 cells through the mitochondrial pathway. 1639 3


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