Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Photodynamic therapy (PDT) is a potential tool in cancer treatment. Today this therapy is established among others for the treatment of nonmelanoma skin cancer. However, the more dangerous skin cancer--the melanoma--still has to be removed by surgery. Therefore, we investigated the effects of PDT and additional administration of heme oxygenase I (HO-I) and poly(ADP-ribose) polymerase (PARP) inhibitors on the treatment of melanoma cells in comparison to nonmalignant keratinocytes. Therefore, cocultures were established with WM451LU melanoma cells and HaCaT keratinocytes. In the coculture some 65% melanoma cells and 35% HaCaT cells were present before PDT, whereas after PDT the proportion was 41% melanoma cells and 59% HaCaT cells. Combination of both inhibitors improves these results to only 16% melanoma cells and 84% HaCaT cells. PDT is, therefore, a potent skin cancer treatment, which might also be interesting for melanoma treatment. The cytotoxic effects of PDT are largely mediated by ROS. Addition of HO-I and PARP inhibitors could improve the efficiency of photodynamic treatment.
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PMID:Combination of PDT and inhibitor treatment affects melanoma cells and spares keratinocytes. 2107 85

UV radiation (UVR) induces DNA damage, leading to the accumulation of mutations in epidermal keratinocytes and immunosuppression, which contribute to the development of nonmelanoma skin cancer. We reported previously that the TLR4-MyD88 signaling axis is necessary for UV-induced apoptosis. In the dinitrofluorobenzene contact hypersensitivity model, UV-irradiated MyD88-deficient (MyD88(-/-)) C57BL/6 mice had intact ear swelling, exaggerated inflammation, and higher levels of dinitrofluorobenzene-specific IgG2a compared with wild-type (WT) mice. Even with normal UV-induced, dendritic cell migration, DNA damage in the local lymph nodes was less pronounced in MyD88(-/-) mice compared with WT mice. Cultured, UV-irradiated WT APCs showed cleavage (inactivation) of the DNA damage-recognition molecule PARP, whereas PARP persisted in MyD88(-/-) and TLR4(-/-) APCs. Epidermal DNA from in vivo UV-irradiated MyD88(-/-) mice had an increased resolution rate of cyclobutane pyrimidine dimers. Both in vitro treatment of MyD88(-/-) APCs with and intradermal in vivo injections of PARP inhibitor, PJ-34, caused WT-level cyclobutane pyrimidine dimer repair. Lymphoblasts deficient in DNA repair (derived from a xeroderma pigmentosum group A patient) failed to augment DNA repair after MyD88 knockdown after UVR, in contrast to lymphoblasts from a healthy control. These data suggest that interference with the TLR4/MyD88 pathway may be a useful tool in promoting DNA repair and maintaining immune responses following UVR-induced damage.
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PMID:Ultraviolet radiation signaling through TLR4/MyD88 constrains DNA repair and plays a role in cutaneous immunosuppression. 2571 94

Honokiol, a plant lignan has been shown to have antineoplastic effects against nonmelanoma skin cancer developments in mice. In this study, antineoplastic effects of honokiol were investigated in malignant melanoma models. In vitro effects of honokiol treatment on SKMEL-2 and UACC-62 melanoma cells were evaluated by measuring the cell viability, proliferation, apoptosis, cell cycle analysis, and expressions of various proteins associated with cell cycle progression and apoptosis. For the in vivo study, male nude mice inoculated with SKMEL-2 or UACC-62 cells received injections of sesame oil or honokiol for two to seven weeks. In vitro honokiol treatment caused significant decrease in cell viability, proliferation, cell cycle arrest, increased apoptosis, and modulation of apoptotic and cell cycle regulatory proteins. Honokiol caused an accumulation of cells in the G2/M phase of the cell cycle in SKMEL-2 and G0/G1 phase in UACC-62 cells. An elevated level of caspases and PARP were observed in both cell lines treated with honokiol. A decrease in the expression of various cell cycle regulatory proteins was also observed in honokiol treated cells. Honokiol caused a significant reduction of tumor growth in SKMEL-2 and UACC-62 melanoma xenografts. These findings suggest that honokiol is a good candidate for further studies as a possible treatment for malignant melanoma.
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PMID:Antineoplastic Effects of Honokiol on Melanoma. 2819 18