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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular stressors induce various outcomes including inhibition of cell proliferation and cell death. Sodium salicylate (SA), a plant stress hormone, can suppress the proliferation or cause apoptosis in certain mammalian cancer cells. Plant stress hormones are activators of cellular responses, including cell death, to diverse stress situations in plants. Thus, we hypothesized that plant stress hormones share the ability to adversely affect cancer cells. We found that the plant stress hormone SA suppressed proliferation of lymphoblastic leukemia, prostate, breast and melanoma human cancer cells. Jasmonic acid (JA), a plant stress hormone belonging to the Jasmonate family, induced death in lymphoblastic leukemia cells and caused suppression of cell proliferation in the other human cancer cells mentioned above. Another member of the Jasmonate family, methyl jasmonate (MJ), induced death in each of the cell lines. Plant stress hormones did not affect normal human lymphocytes, in contrast to their strong effect on lymphoblastic leukemia cells. JA and MJ caused apoptotic death, as determined by characteristic nuclear morphology, flow cytometric DNA profile and elevation of caspase-3 activity. Finally, mice bearing EL-4 lymphoma and treated with MJ, survived for significantly (P = 0.00953) longer periods of time than untreated mice. These findings suggest that plant stress hormones may potentially be a novel class of anti-cancer drugs.
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PMID:Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells. 1196 Mar 40

The benzoacronycine derivative S23906-1 is a highly potent antitumor agent with a broad spectrum of activity against different human solid tumor xenografts. The marked cytotoxic potential of this drug may be the result of its interaction with DNA but the precise mechanism of action remains unclear at present. We have investigated the induction of apoptosis in human promyelocytic leukemia HL-60 and murine melanoma B16 cells treated with S23906-1. With both cell lines, the drug induces cell cycle perturbations (G2/M arrest) and triggers apoptosis as revealed by the externalization of Annexin V-targeted PS residues at the periphery of the cells. But the biochemical pathways leading to apoptosis are different for the two cancer cell lines. In HL-60 cells, the drug induces significant variations of the Delta Psi(mt), measured by flow cytometry using the fluorochromes JC-1 and cm-X-ros. Activation of caspase-3 and chromatin condensation in HL-60 cells exposed to submicromolar concentrations of S23906-1 for 24hr were also clearly seen by flow cytometry and confocal microscopy experiments. In contrast, the extent of apoptosis induced by S23906-1 was found to be much more limited in B16 cells. No significant variations of Delta Psi(mt) and no cleavage of the fluorescent caspase-3 substrate GDEVDGI (PhiPhiLux-G(1)D(2) probe) could be detected by cytometry in B16 cells exposed to S23906-1. In addition, we characterized the mitochondrial production of reactive oxygen species (ROS) using the probe dihydroethidine (HE) and the variations of the mitochondrial mass using the cardiolipin-interacting probe nonyl acridine orange (NAO). S23906-1 stimulates the production of ROS in both cell lines but the number of mitochondria seems to increase only in drug-treated B16 cells. Collectively these findings identify S23906-1 as a potent inducer of cell apoptosis in the leukemia cells and to a lower extent in the melanoma cells. The results help to understand the downstream cytotoxic actions of this new anticancer agent which is currently undergoing preclinical development.
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PMID:Induction of apoptosis in HL-60 leukemia and B16 melanoma cells by the acronycine derivative S23906-1. 1199 85

A family of phenotypically and biologically different transplantable hamster melanomas was derived from a single tumor more than 40 yr ago. In this work, we were seeking the differences between the abilities of the cells from two biologically heterogeneous (melanotic and amelanotic) members of this family to undergo spontaneous or camptothecin-induced apoptosis. We studied these differences by looking at three important features of the apoptotic process, i.e. binding of annexin V, DNA fragmentation and caspase-3 activity. Of these, annexin binding and DNA fragmentation were more pronounced in the parental, melanotic line while the activity of caspase-3 was stronger in the amelanotic tumor cells. We concluded that a spontaneous alteration of the original, melanotic melanoma line into an amelanotic one, associated with more aggressive tumor progression, was accompanied by significant decrease in ability to undergo spontaneous and camptothecin-induced apoptosis, and that apoptosis of these two cell types may not depend on the activity of caspase-3.
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PMID:Heterogeneous susceptibility to spontaneous and induced apoptosis characterizes two related transplantable melanomas with different biological properties. 1202 88

Deprivation of tyrosine (Tyr) and phenylalanine (Phe) inhibits growth and induces programmed cell death (apoptosis) of human A375 melanoma cells. Herein, we found that activation of caspases and release of mitochondrial cytochrome c are required for this process. Culturing A375 cells in Tyr/Phe-free medium, containing 10% dialyzed fetal bovine serum, results in activation of caspase-3-like activity. This is accompanied by decreased cell viability and increased apoptosis. Tyr/Phe deprivation also stimulates proteolytic cleavage of the DNA repair enzyme, poly(ADP-ribose) polymerase (PARP). Western blot analysis showed that caspases 3, 7, 8, and 9 are activated by deprivation of Tyr/Phe. Tyr/Phe deprivation decreases mitochondrial membrane potential, induces cleavage of Bid, increases translocation of Bax from the cytosol to mitochondria, and results in release of cytochrome c from the mitochondria to the cytosol. Apoptosis due to Tyr/Phe deprivation is almost completely inhibited by the broad-spectrum cell-permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z.VAD.fmk). This inhibitor suppresses the cleavage of Bid, the release of cytochrome c from the mitochondria to the cytosol, and the cleavage of PARP. Decylubiquinone, a mitochondrial permeability transition pore inhibitor, does not suppress the activation of caspase 8 but suppresses release of cytochrome c, activation of caspase 9, and induction of apoptosis. These results indicate that activation of caspases, cleavage of Bid, and mitochondrial release of cytochrome c are required for apoptosis induced by Tyr/Phe deprivation.
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PMID:Activation of caspases and cleavage of Bid are required for tyrosine and phenylalanine deficiency-induced apoptosis of human A375 melanoma cells. 1206 1

All human melanoma cell lines (assessed by annexin V and TUNEL assays) were resistant to apoptosis induction by TRAIL/Apo2L protein. TRAIL/Apo2L activated caspase-8 and caspase-3, but subsequent apoptotic events such as poly(ADP-ribose) polymerase cleavage and DNA fragmentation were not observed. To probe the molecular mechanisms of cellular resistance to apoptosis, melanoma cell lines were analyzed for expression of apoptosis regulators (apoptotic protease-associated factor-1, FLIP, caspase-8, caspase-9, caspase-3, cellular inhibitor of apoptosis, Bcl-2, or Bax); no correlation was observed. TRAIL/Apo2L was induced in melanoma cell lines by IFN-beta and had been correlated with apoptosis induction. Because IFN-beta induced other gene products that have been associated with apoptosis, it was postulated that one or more IFN-stimulated genes might sensitize cells to TRAIL/Apo2L. Melanoma cell lines were treated with IFN-beta for 16-24 h before treatment with TRAIL/Apo2L. Regardless of their sensitivity to either cytokine alone, >30% of cells underwent apoptosis in response to the combined treatment. Induction of apoptosis by IFN-beta and TRAIL/Apo2L in combination correlated with synergistic activation of caspase-9, a decrease in mitochondrial potential, and cleavage of poly(ADP-ribose) polymerase. Cleavage of X-linked inhibitor of apoptosis following IFN-beta and TRAIL/Apo2L treatment was observed in sensitive WM9, A375, or WM3211 cells but not in resistant WM35 or WM164 cells. Thus, in vitro IFN-beta and TRAIL/Apo2L combination treatment had more potent apoptotic and anti-growth effects when compared with either cytokine alone in melanoma cells lines.
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PMID:IFN-beta pretreatment sensitizes human melanoma cells to TRAIL/Apo2 ligand-induced apoptosis. 1209 88

Ceramide is implicated in the regulation of various signaling pathways leading to proliferation, differentiation or apoptotic cell death, but there have been few investigations about the effects of ceramide on the cell growth and the melanogenesis of melanocytes. In the present study, we investigated the effects of cell-permeable ceramide on Malme-3M human melanoma cell line. MTT proliferation assay showed that C2-ceramide inhibited the growth of Malme-3M cells in a dose-dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase and an increase in the G0/G1 phase. Flow cytometric analysis for apoptotic cells and morphological observations indicated that the antiproliferative effect of C2-ceramide was not due to apoptosis. We next investigated the effects of C2-ceramide on the pigmentation of Malme-3M melanoma cells. The results showed that C2-ceramide induced only a slight decrease of tyrosinase activity and melanin synthesis. To investigate the ceramide signaling pathway, we studied the influence of C2-ceramide on extracellular signal-regulated kinase (ERK) and Akt activation by Western blot. We demonstrated that the amount of phosphorylated Akt was decreased by C2-ceramide, whereas ERK was activated transiently. Because of a well-known involvement of ceramide in apoptosis, we further investigated the level of caspase-3 and HSP70 after treatment of C2-ceramide. We found that the caspase-3 was not activated and the expression of HSP70 increased moderately. In conclusion, C2-ceramide inhibited the cell growth of Malme-3M cells without the induction of apoptosis. We suggest that increased HSP70 may be related to the resistance against apoptosis.
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PMID:Effects of C2-ceramide on the Malme-3M melanoma cell line. 1235 15

Many experiments have demonstrated that some cell lines are resistant to chemically induced apoptosis in vitro, and that apoptosis itself is far from being a homogenous phenomenon. Here we show that 10 microg/ml etoposide elicited only minor changes in Bowes human melanoma cells (temporary decrease in cell viability and proliferation, transient phospatidylserine externalization and caspase-3 activation), which weren't clearly capable to start apoptotic pathway in the entire treated population. On the other hand, potassium chromate at concentration of 150 microg/ml executed cell death bearing some features of apoptosis (cell blebbing, caspase-3 activation and cytoskeletal changes) but lacking or showing weakly others (DNA fragmentation and phospatidylserine externalization). Our results suggest that in detecting apoptosis several fault-proof detection systems are to be used to avoid misleading results and conclusions in each experimental setting.
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PMID:Time dependent appearance of selected apoptotic markers and usefulness of their detection in vitro. 1258 80

Survivin is a structurally unique member of the inhibitors of apoptosis protein family and is involved in the control of cell division and inhibition of apoptosis. The notion that survivin is overexpressed in most human tumors but absent in normal adult tissues with only a few exceptions has led to the proposal of survivin as a promising therapeutic target for novel anticancer therapies. In this context, we generated a hammerhead ribozyme targeting the 3' end of the CUA110 triplet in the survivin mRNA. Two human melanoma cell lines (JR8 and M14) overexpressing survivin were stably transfected with the pRc/CMV vector carrying the ribozyme sequence. Two polyclonal cell populations proven to endogenously express ribozyme and characterized by a markedly lower survivin protein level (-60% and -50%, respectively) than JR8 and M14 parental cells were selected for the study. Ribozyme-expressing cells showed a significantly (p<0.01) increased sensitivity to gamma-irradiation (as detected by clonogenic cell survival) compared to JR8 and M14 cells. Moreover, in the JR8 cell line, the extent of radiation-induced apoptosis (in terms of percentage of apoptotic nuclei in cells stained with propidium iodide and level of caspase-3 catalytic activity) was markedly greater in ribozyme-expressing cells than in parental cells. These results demonstrate for the first time that attenuation of survivin expression renders human melanoma cells more susceptible to gamma-irradiation.
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PMID:Radiosensitization of human melanoma cells by ribozyme-mediated inhibition of survivin expression. 1264 30

Tissue inhibitors of metalloproteinases (TIMPs) are important regulators of matrix metalloproteinase (MMP) and adamalysin (ADAM) activity. We have previously shown that adenovirally expressed tissue inhibitor of metalloproteinases-3 (TIMP-3) induces apoptosis in melanoma cells and inhibits growth of human melanoma xenografts. Here, we have studied the role of death receptors in apoptosis of melanoma cells induced by TIMP-3. Our results show, that the exposure of three metastatic melanoma cell lines (A2058, SK-Mel-5, and WM-266-4) to recombinant TIMP-3, N-terminal MMP inhibitory domain of TIMP-3, as well as to adenovirally expressed TIMP-3 results in stabilization of tumor necrosis factor receptor-1 (TNF-RI), FAS, and TNF-related apoptosis inducing ligand receptor-1 (TRAIL-RI) on melanoma cell surface and sensitizes these cells to apoptosis induced by TNF-alpha, anti-Fas-antibody and TRAIL. Stabilization of death receptors by TIMP-3 results in activation of caspase-8 and caspase-3, and subsequent apoptosis is blocked by specific caspase-8 inhibitor (Z-IETD-FMK) and by pan-caspase inhibitor (Z-DEVD-FMK). Adenovirus-mediated expression of TIMP-3 in human melanoma xenografts in vivo resulted in increased immunostaining for TNF-RI, FAS, and cleaved caspase-3, and in apoptosis of melanoma cells. Taken together, these results show that TIMP-3 promotes apoptosis in melanoma cells through stabilization of three distinct death receptors and activation of their apoptotic signaling cascade through caspase-8.
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PMID:Tissue inhibitor of metalloproteinases-3 induces apoptosis in melanoma cells by stabilization of death receptors. 1268 14

Extensive labelling for the apoptotic markers calcium channel receptor P2X(7) and caspase-3 and telomerase activity was co-localized at a similar intensity in areas affected by superficial spreading melanoma obtained from 80 patients. Labelling for each of these markers also extended 2 microm from the melanoma into the keratinocyte layer of the adjacent normal epidermis. Conversely, the calcium-regulating receptors P2X(1-3) and P2Y(2) (found in normal but not neoplastic skin) were fully de-expressed within 2 microm of the melanoma but fully expressed beyond that distance. The cell adhesion protein E-cadherin (also only present in normal skin) was progressively de-expressed from a point 2 microm from the melanoma until full de-expression within the lesion. These results show that telomerase-induced proliferation and defensive apoptosis are co-localized and simultaneous processes in melanoma tissue. Melanoma cell proliferation appears to overwhelm the apoptotic defence, perhaps due to the anti-apoptotic effects of telomerase. In addition, keratinocyte regulation of the epidermis and dermis is severely compromised by the loss of E-cadherin and P2X(1-3) and P2Y(2) receptors, resulting in a lesion that is aggressive and malignant.
Melanoma Res 2003 Apr
PMID:Increased expression of apoptotic markers in melanoma. 1269 Feb 96


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