Cell-type dependent response of melanoma cells to aloe emodin.
Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H(2)O(2) production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy.
Department of Immunology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
J
J
Radovic
D
D
Maksimovic-Ivanic
G
G
Timotijevic
S
S
Popadic
Z
Z
Ramic
V
V
Trajkovic
D
D
Miljkovic
S
S
Stosic-Grujicic
S
S
Mijatovic
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D020935:MAP Kinase Signaling System; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000880:Anthraquinones; D017382:Reactive Oxygen Species; C518327:aloe emodin; D052247:Nitric Oxide Synthase Type II