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Open AccessArticle

Petromurin C Induces Protective Autophagy and Apoptosis in FLT3-ITD-Positive AML: Synergy with Gilteritinib

1
Department of Pharmacy, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08626, Korea
2
Laboratoire de Biologie Moléculaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg
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Service d’Histologie, Faculté de Médicine, Université de Lorraine, INSERM U1256 NGERE, 54000 Nancy, France
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ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
5
Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), Terminal de Cruzeiros do Porto de Lexões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(1), 57; https://doi.org/10.3390/md18010057
Received: 14 December 2019 / Revised: 9 January 2020 / Accepted: 10 January 2020 / Published: 16 January 2020
Treatment of acute myeloid leukemia (AML) remains inefficient due to drug resistance and relapse, particularly in patients with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD). Marine-derived natural products have recently been used for drug development against AML. We show in this study that petromurin C, which was isolated from the culture extract of the marine-derived fungus Aspergillus candidus KUFA0062, isolated from the marine sponge Epipolasis sp., induces early autophagy followed by apoptotic cell death via activation of the intrinsic cell death pathway concomitant with mitochondrial stress and downregulation of Mcl-1 in FLT3-ITD mutated MV4-11 cells. Moreover, petromurin C synergized with the clinically-used FLT3 inhibitor gilteritinib at sub-toxic concentrations. Altogether, our results provide preliminary indications that petromurin C provides anti-leukemic effects alone or in combination with gilteritinib. View Full-Text
Keywords: acute myeloid leukemia; Aspergillus candidus; Epipolasis sp.; cell death; mitochondrial stress; combination treatment acute myeloid leukemia; Aspergillus candidus; Epipolasis sp.; cell death; mitochondrial stress; combination treatment
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MDPI and ACS Style

Ha, Y.N.; Song, S.; Orlikova-Boyer, B.; Cerella, C.; Christov, C.; Kijjoa, A.; Diederich, M. Petromurin C Induces Protective Autophagy and Apoptosis in FLT3-ITD-Positive AML: Synergy with Gilteritinib. Mar. Drugs 2020, 18, 57.

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