Transcription profiling of the Neurospora crassa response to a group of synthetic (thio)xanthones and a natural acetophenone.
Xanthones are a class of heterocyclic compounds characterized by a dibenzo-γ-pyrone nucleus. Analysis of their mode of action in cells, namely uncovering alterations in gene expression, is important because these compounds have potential therapeutic applications. Thus, we studied the transcriptional response of the filamentous fungus Neurospora crassa to a group of synthetic (thio)xanthone derivatives with antitumor activity using high throughput RNA sequencing. The induction of ABC transporters in N. crassa, particularly atrb and cdr4, is a common consequence of the treatment with xanthones. In addition, we found a group of genes repressed by all of the tested (thio)xanthone derivatives, that are evocative of genes downregulated during oxidative stress. The transcriptional response of N. crassa treated with an acetophenone isolated from the soil fungus Neosartorya siamensis shares some features with the (thio)xanthone-elicited gene expression profiles. Two of the (thio)xanthone derivatives and the N. siamensis-derived acetophenone inhibited the growth of N. crassa. Our work also provides framework datasets that may orientate future studies on the mechanisms of action of some groups of xanthones.
ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal ; IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
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Pedro Gonçalves
IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Nuno
N
Silva
ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Carla
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Oliveira
Plant and Microbial Biology Department, The University of California, Berkeley, CA 94720, USA.
David J
DJ
Kowbel
Plant and Microbial Biology Department, The University of California, Berkeley, CA 94720, USA.
N Louise
NL
Glass
ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal ; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal.
Anake
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Kijjoa
Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal ; Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Andreia
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Palmeira
Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal ; Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal ; Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Emília
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Sousa
Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal ; Centro de Química Medicinal da Universidade do Porto (CEQUIMED-UP), University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal ; Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Madalena
M
Pinto
ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal ; IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal ; Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
Arnaldo
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Videira
ABC transporters; Acetophenone; CZT-1; Neurospora crassa; Transcriptional profiling; Xanthones