Track topics on Twitter Track topics that are important to you
Melanoma is resistant to most standard chemotherapeutics. We analysed the combined effect of doxorubicin and enzastaurin on cell death of four melanoma cell lines, namely G361, SK-MEL3, A375 and SAN. Enzastaurin IC50 was calculated by measure of growth inhibition with MTS assay and corresponded to 2 μM; the half maximal cytotoxicity of doxorubicin was obtained at 3μM dose. Evaluation of combination index showed synergism (CI>1) or additive effect (CI=1) with all melanoma cell lines, with enzastaurin doses >0.6 μM and doxorubicin doses > 1μM. Combination of the two drugs resulted in increase in caspase 3 and 8 activation, in comparison with activation by single agents. Caspase 8 activation was impaired by TNFR-1 blocking. Our results show doxorubicin stimulated production of TNFα, whereas enzastaurin stimulated TNFR-1 expression on plasmamembrane. The effect on TNFR-1 appeared to be mediated by PKCζ inhibition. Taken together, our findings suggest enzastaurin increases doxorubicin-induced apoptosis of melanoma by a mechanism involving, at least in part, activation of the TNF-α signal. This article is protected by copyright. All rights reserved.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Federico II University, Napoli, Italy.
This article was published in the following journal.
Name: Pigment cell & melanoma research
Mutations in the NRAS oncogene are present in up to 20% of melanoma. Here, we show that interferon alpha-inducible protein 6 (IFI6) is necessary for NRASQ61K-induced transformation and melanoma growth...
In the current study we examined the ability of 4-methylumbelliferone (4-MU), which can inhibit hyaluronic acid synthesis, to sensitize K562 chronic myelogenous leukemia (CML) cells to doxorubicin the...
PERP (p53 apoptosis effector related to PMP-22), a transcriptional target of p53, is downregulated and contributes to the impairment of apoptosis in uveal melanoma (UM). Intriguingly, PERP is not indu...
Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field ...
Doxorubicin (Dox) is extensively used for chemotherapy in different types of cancer, but its use is limited to because of its cardiotoxicity. Our previous studies found that doxorubicin-induced insuli...
This study will collect further basic safety data on patients with cancer treated with enzastaurin. This study is not open to the public. The purpose of the this study is to extend the c...
The purpose of the protocol is to induce a novel radiochemotherapy with enzastaurin as first-line treatment regimen in glioblastoma: Patients with active, unmethylated MGMT promoter will ...
Reports to date show limited efficacy of immunotherapy for uveal melanoma. Recent experimental and clinical evidence suggests synergy between radiation therapy and immunotherapy. We will e...
This clinical research study is to investigate the prevention of relapse in patients with diffuse large B cell lymphoma (DLBCL) using enzastaurin daily. This is a randomised trial which c...
The primary objective of this study is to see if enzastaurin affects the pGSK3 beta level in B-cell chronic lymphocytic leukemia (B-CLL) cells.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
An unpigmented malignant melanoma. It is an anaplastic melanoma consisting of cells derived from melanoblasts but not forming melanin. (Dorland, 27th ed; Stedman, 25th ed)
A secreted tumor necrosis factor receptor family member that has specificity for TNF-RELATED APOPTOSIS-INDUCING LIGAND. It plays a modulating role in activation of APOPTOSIS signaling.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
Melanoma is a highly malignant tumor of melanin-forming cells (melanocytes) There are most commonly found in the skin (resulting from sunlight exposure), but also in the eyes and mucous membranes. Metastasis to other regions of the body is also common....
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...