UNIPROT:P42574 - FACTA Search

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Query: UNIPROT:P42574 (caspase-3)
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Liverwort constituents have been reported to exert a broad spectrum of biological activities. In this study, we used a bioactivity-guided separation of an extract from the liverwort species Marchantia emarginata subsp. tosana to determine its anticancer activity. A high level of the active ingredient was isolated from this liverwort and its chemical structure was identified and characterized by various spectra. It was found to be identical to a well-known compound, marchantin A, a cyclic bisbibenzyl ether. However, no anticancer activities of this compound have previously been reported. We found that marchantin A efficiently induced cell growth inhibition in human MCF-7 breast cancer cells, with an IC(50) of 4.0microg/mL. Fluorescence microscopy and a Western blot analysis indicated that marchantin A actively induced apoptosis of MCF-7 cells. The levels of cleaved caspase-8, cleaved caspase-3, cleaved caspase-9, and cleaved poly (ADP ribose) polymerase (PARP) increased. However, the level of Bid markedly decreased in a dose- and time-dependent manner. We also evaluated the anticancer activities of marchantin A on the regulation of cell cycle regulators such as p21, p27, cyclin B1, and cyclin D1. The p21 and p27 gene expressions increased markedly while cyclin B1 and D1 gene expression decreased markedly by treatment with marchantin A. Many report demonstrated that liverwort was suggested to possess potent antioxidant activity. Our results indicate that marchantin A possesses free radical-scavenging activity (EC(50)=20microg/mL). Taken together, for the first time, the compound marchantin A from liverworts demonstrated to be a potent inducer of apoptosis in MCF-7 cells.
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PMID:Marchantin A, a cyclic bis(bibenzyl ether), isolated from the liverwort Marchantia emarginata subsp. tosana induces apoptosis in human MCF-7 breast cancer cells. 1991 53

Treatment of p53(-/-) mice orally with caffeine, voluntary exercise or their combination for 2 weeks prior to a single irradiation with UVB (i) decreased the weight of the epididymal fat pads by 22, 40 and 56%, (ii) decreased the thickness of the dermal fat layer by 10, 26 and 42%, (iii) increased the number of apoptotic sunburn cells by 29, 100 and 489%, (iv) increased the number of caspase-3-positive cells by 33, 117 and 667% and (v) increased the number of mitotic cells with cyclin B1-positive staining by 40, 210 and 510%, respectively. Pearson's correlation coefficient indicated a statistically significant inverse relationship between the level of tissue fat and the number of mitotic cells with cyclin B1 in p53(-/-) mice but not in p53(+/+) littermates. Western blot analysis indicated that treatment of p53(-/-) mice with caffeine together with exercise increased the level of cyclin B1 significantly more than in p53(+/+) mice. p53(-/-) mice, but not p53(+/+) mice, treated with caffeine during exercise exhibited a dramatic decrease in the level of survivin. Our results suggest that voluntary exercise in combination with oral caffeine may exert a synergistic increase in UVB-induced apoptosis and that tissue fat may be a more important modulator of apoptosis and carcinogenesis in p53-deficient mice than in p53-normal mice. The stimulatory effects on apoptosis in p53(-/-) mice by the combination treatment might be associated with increased levels of cyclin B1 and decreased levels of survivin.
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PMID:Oral administration of caffeine during voluntary exercise markedly decreases tissue fat and stimulates apoptosis and cyclin B1 in UVB-treated skin of hairless p53-knockout mice. 1992 39

Aloe-emodin (AE), a natural, biologically active compound from the rhizome of Rheum palmatum, has been shown to induce apoptosis in several cancer cell lines in vitro. However, its molecular mechanism of action in the apoptosis induction of human nasopharyngeal carcinoma (NPC) cells has not been explored. This study shows that AE induced G(2)/M phase arrest by increasing levels of cyclin B1 bound to Cdc2, and also caused an increase in apoptosis of NPC cells, which was characterized by morphological changes, nuclear condensation, DNA fragmentation, caspase-3 activation, cleavage of poly (ADP-ribose) polymerase (PARP) and increased sub-G(1) population. Treatment of NPC cells with AE also resulted in a decrease in Bcl-X(L) and an increase in Bax expression. Ectopic expression of Bcl-X(L) but not Bcl-2 or small interfering RNA (siRNA)-mediated attenuation of Bax suppressed AE-induced apoptotic cell death. AE-induced loss of mitochondrial membrane potential (MMP) and increase in cellular Ca(++) content, reactive oxygen species (ROS) and apoptotic cell death were suppressed by the treatment of cyclosporin A (CsA) or caspase-8 inhibitor Z-IETD-FMK. Co-treatment with caspase-9 inhibitor Z-LEHD-FMK could inhibit AE-induced cell death and the activation of caspase-3 and -9. In addition, suppression of caspase-8 with the specific inhibitor Z-IETD-FMK inhibited AE-induced the activation of Bax, the cleavage of Bid, the translocation of tBid to the mitochondria and the release of cytochrome c, apoptosis-inducing factor (AIF) and Endo G from the mitochondria and subsequent apoptosis. Taken together, these results indicate that the caspase-8-mediated activation of the mitochondrial death pathway plays a critical role in AE-induced apoptosis of NPC cells.
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PMID:Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway. 1994 42

Previous studies have shown that microRNAs (miRNAs) can control steroidogenesis in cultured granulosa cells. In this study we wanted to determine if miRNAs can also affect proliferation and apoptosis in human ovarian cells. The effect of transfection of cultured primary ovarian granulosa cells with 80 different constructs encoding human pre-miRNAs on the expression of the proliferation marker, PCNA, and the apoptosis marker, Bax was evaluated by immunocytochemistry. Eleven out of 80 tested miRNA constructs resulted in stimulation, and 53 miRNAs inhibited expression of PCNA. Furthermore, 11 of the 80 miRNAs tested promoted accumulation of Bax, while 46 miRNAs caused a reduction in Bax in human ovarian cells. In addition, two selected antisense constructs that block the corresponding miRNAs mir-15a and mir-188 were evaluated for their effects on expression of PCNA. An antisense construct inhibiting mir-15a (which precursor suppressed PCNA) increased PCNA, whereas an antisense construct for mir-188 (which precursor did not change PCNA) did not affect PCNA expression. Verification of effects of selected pre-mir-10a, mir-105, and mir-182 by using other markers of proliferation (cyclin B1) and apoptosis (TdT and caspase 3) confirmed specificity of miRNAs effects on these processes. This is the first direct demonstration of the involvement of miRNAs in controlling both proliferation and apoptosis by ovarian granulose cells, as well as the identification of miRNAs promoting and suppressing these processes utilizing a genome-wide miRNA screen.
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PMID:Identification of microRNAs controlling human ovarian cell proliferation and apoptosis. 2003 79

The heavy metals lead (Pb) and mercury (Hg) pose potential risks to sustainability of environment and thus to our future generations. General objective of this in vitro study was to examine the secretory activity of porcine ovarian granulosa cells after Pb and Hg administration and to outline the potential intracellular mediators of its effects. For this purpose, release of insulin-like growth factor I (IGF-I) and steroid hormone progesterone (P(4)), expression of proliferation- related (cyclin B1) and apoptosis-related (caspase-3) peptides was examined in porcine ovarian granulosa cells after heavy metals administration. Obtained data indicate Pb-induced inhibition of IGF-I release at lower doses (0.063 mg/mL and 0.046 mg/mL) by ovarian granulosa cells. However, P(4) release was not influenced by Pb addition, while the expression of cyclin B1 and caspase-3 was induced by Pb addition. These results indicate that Pb can affect the pathway of proliferation and apoptosis of porcine ovarian granulosa cells through intracellular substances such as cyclin B1 and caspase-3. On the other hand, the P(4) release by ovarian granulosa cells of pregnant gilts was stimulated by experimental Pb administration at doses of 0.25 mg/mL and 0.063 mg/mL and experimental Hg administration at doses 0.25 mg/mL and 0.083 mg/mL. P(4) release by ovarian cells of pregnant gilts was not influenced by a combinatory dose of FSH (1.0 ng/mL) + Pb (0.083 mg/mL) + Hg (0.083 mg/mL) but it was inhibited by experimental administration of FSH (10 ng/mL) + Pb (0.25 ng/mL) + Hg (0.25 ng/mL). Possible involvement of heavy metals - Pb and Hg and pituitary hormone FSH, in the regulation of P(4) release by porcine ovarian granulosa cells of pregnant gilts was noted. Data obtained from in vitro studies suggest the dose dependent association of heavy metals administration with the hormonal release by porcine ovarian granulosa cells. This association also depended on pregnancy of the gilts.
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PMID:In vitro study on the effects of lead and mercury on porcine ovarian granulosa cells. 2039 Aug 73

Cobalt (Co) is an essential element. The general objective of this in vitro study was to examine dose-dependent changes in the secretory activity of porcine ovarian granulosa cells after experimental Co administration and to outline the potential intracellular mediators of its effects. Concentrations of IGF-I and progesterone were determined by RIA and expression of cyclin B1 and caspase-3 by immunocytochemistry. IGF-I release by granulosa cells was stopped by Co addition at the concentration 1 mg/mL. Progesterone release by granulosa cells was decreased at the lowest Co addition (0.09 mg/mL). In our study the changes of the expression of proliferation related peptide cyclin B1 and apoptosis related peptide caspase-3 in ovarian granulosa cells was observed after experimental Co addition. The molecular pathways stimulated by Co through the expression of cyclin B1 and caspase-3 were found. In conclusion, this study provides novel evidence that cobalt is the factor which can initiate adverse effects in ovarian granulosa cells. These results contribute towards the understanding of mechanisms relating to endocrine disruptor-induced alterations in porcine ovarian granulosa cells.
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PMID:Cobalt-induced changes in the IGF-I and progesterone release, expression of proliferation- and apoptosis-related peptides in porcine ovarian granulosa cells in vitro. 2039 87

The aim of our studies was to compare the roles of leptin and ghrelin in the direct control of proliferation, apoptosis, and secretory activity by porcine ovarian cells. In our in vitro experiments, we analyzed the effects of leptin and ghrelin treatments (at 0, 1, 10, or 100ng/mL medium) on the accumulation of proliferation-related peptides (PCNA, cyclin B1, MAP kinase [MAPK]) and apoptosis-associated peptides (Bax, caspase 3, p53), and on progesterone secretion by cultured porcine granulosa cells, using immunocytochemistry, SDS PAGE-Western immunoblotting, and radioimmunoassay (RIA). Leptin stimulated proliferation (PCNA, cyclin B1, MAPK), apoptosis (Bax, p53), and progesterone secretion. Ghrelin promoted proliferation (PCNA, cyclin B1, MAPK) and progesterone secretion but suppressed apoptosis (Bax, caspase 3, p53). These observations suggest that both leptin and ghrelin directly control proliferation, apoptosis, and secretory activity by porcine ovarian cells. At the level of the ovary, in contrast to the hypothalamo-hypophysial system, leptin and ghrelin may have similar action in promoting granulosa cell proliferation and progesterone secretion, but they may be antagonistic to one another (leptin, stimulator; ghrelin, inhibitor) in controlling apoptosis.
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PMID:Comparison of effects of leptin and ghrelin on porcine ovarian granulosa cells. 2045 67

The incidence of thyroid cancer increases with age, and it is twice in women as common as in men. The undifferentiated thyroid cancer (UTC) is the most aggressive of all thyroid cancers. Unfortunately, there are almost no efficacious therapeutic modalities. It is important to develop some new effective therapies. Evodiamine is a chemical extracted from a kind of Chinese herb named Wu-Chu-Yu and has been demonstrated to be effective in preventing the growth of a variety of cancer cells. In the present study, the mechanism by which evodiamine inhibited the undifferentiated thyroid cancer cell line ARO was examined. Based on 3-(4,5-dimethylthiazol -2-yle)2,5-diphenyltetrazolium bromide (MTT) assay, cell proliferation rate was reduced dose-dependently by evodiamine, but not by rutaecarpine. According to the flow cytometric analysis, evodiamine treatment resulted in G2/M arrest and DNA fragmentation in ARO cells. The G2/M arrest was accompanied with an increase of the expression of cdc25C, cyclin B1, and cdc2-p161 protein, and it was also with a decrease of the expression of cdc2-p15. Furthermore, by using the TUNEL assay, evodiamine-induced apoptosis was observed at 48 h and extended to 72 h. Western blotting demonstrated that evodiamine treatment induced the activation of caspase-8, caspase-9, caspase-3, and the cleavage of poly ADP-ribose polymerase (PARP). These results suggested that evodiamine inhibited the growth of the ARO cells, arrested them at M phase, and induced apoptosis through caspases signaling.
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PMID:Anti-proliferative effects of evodiamine on human thyroid cancer cell line ARO. 2050 48

The aim of the present study was to understand the interrelationships between stress, hormones and basic ovarian functions in the ovary. For this purpose, we compared the expression of markers of proliferation (PCNA, cyclin B1), of apoptosis (Bax, caspase-3) and secretory activity (release of progesterone, P(4), and insulin-like growth factor, IGF-I) in whole ovarian follicles and granulosa cells cultured in conditions of normal temperature (37.5 degrees C) and feeding (with serum), high temperature (41.5 degrees C, with serum) and malnutrition (37.5 degrees C, without serum), with and without hormones [IGF-I, leptin and follicle-stimulating hormone (FSH)]. The expression of proliferation and apoptosis markers was evaluated by SDS PAGE-western blotting whereas radioimmunoassay (RIA) measured the release of hormones. High temperature dramatically induced a reduction in both proliferation and apoptosis markers in both ovarian follicles and granulosa cells and induced a significant increase in P(4) and IGF-I release by ovarian granulosa cells but not in P(4) secretion by ovarian follicles. Serum deprivation increased accumulation of cyclin B1 but not other markers of proliferation (PCNA) and apoptosis (Bax, caspase-3) or P(4) release in ovarian follicles. On the contrary, it inhibited the expression of apoptotic marker (Bax), release of both P(4) and IGF-I but it did not affect proliferation marker (PCNA) in granulosa cells. Adding IGF-I, leptin and FSH affected proliferation, apoptosis and secretory activity of ovarian cell functions but also prevented an inhibitory effect of high temperature on the expression of Bax and PCNA and an inhibitory action of serum deprivation on PCNA in ovarian follicles. Furthermore, treatment with these hormones prevented an inhibitory action of thermal stress on Bax, PCNA, P(4) and IGF-I in ovarian granulosa cells. The present observations (1) confirm the involvement of hormones (IGF-I, leptin and FSH) in the control of proliferation, apoptosis and secretory activity of ovarian cells, (2) demonstrate for the first time that heat stress/increased temperature can induce a reduction in ovarian cell proliferation and apoptosis and an oversecretion of ovarian hormones, (3) show that malnutrition/serum deprivation can reduce both apoptosis and secretory activity of ovarian cells, (4) demonstrate the differences in the response of granulosa and other ovarian follicular cells to stresses, and (5) are the first demonstration that hormones (IGF-I, leptin and FSH) could be used for preventing the effect of stresses on ovarian cell functions.
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PMID:Effect of two types of stress (heat shock/high temperature and malnutrition/serum deprivation) on porcine ovarian cell functions and their response to hormones. 2051 27

Peroxisome proliferator-activated receptor (PPAR)-gamma agonists such as troglitazone, pioglitazone and thiazolidine have been shown to induce apoptosis in human colon cancer cells. The molecular mechanism of PPARgamma agonist-induced apoptosis of colon cancer cells, however, is not clear. Glycogen synthase kinase-3beta (GSK-3beta) is an indispensable element for the activation of nuclear factor-kappa B (NF-kappaB) which plays a critical role in the mediation of survival signals in cancer cells. To investigate the mechanisms of PPARgamma agonist-induced apoptosis of colon cancer cells, we examined the effect of troglitazone (0-16muM) on the activation of GSK-3beta and NF-kappaB. Our study showed that the inhibitory effect of troglitazone on colon cancer cell growth was associated with inhibition of NF-kappaB activity and GSK-3beta expression in a dose-dependent manner. Cells were arrested in G(0)/G(1) phase followed by the induction of apoptosis after treatment of troglitazone with concomitant decrease in the expression of the G(0)/G(1) phase regulatory proteins; Cdk2, Cdk4, cyclin B1, D1, and E as well as in the anti-apoptosis protein Bcl-2 along with an increase in the expression of the pro-apoptosis-associated proteins; Caspase-3, Caspase-9 and Bax. Transient transfection of GSK-3beta recovered troglitazone-induced cell growth inhibition and NF-kappaB inactivation. In contrast, co-treatment of troglitazone with a GSK-3beta inhibitor (AR-a014418) or siRNA against GSK-3beta, significantly augmented the inhibitory effect of troglitazone on the NF-kappaB activity, the cancer cell growth and on the expression of G(0)/G(1) phase regulatory proteins and pro-apoptosis regulatory proteins. These results suggest that the PPARgamma agonist, troglitazone, inhibits colon cancer cell growth via inactivation of NF-kappaB by suppressing GSK-3beta activity.
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PMID:Suppression of NF-kappaB and GSK-3beta is involved in colon cancer cell growth inhibition by the PPAR agonist troglitazone. 2054 Sep 35

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