Journal
MARINE DRUGS
Volume 18, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/md18010057
Keywords
acute myeloid leukemia; Aspergillus candidus; Epipolasis sp.; cell death; mitochondrial stress; combination treatment
Categories
Funding
- NRF [019R1A2C1009231, 2011-0030001]
- Creative-Pioneering Researchers Program at SNU [370C-20160062]
- Televie Luxembourg
- Recherche Cancer et Sang Foundation
- Recherches Scientifiques Luxembourg
- En Haerz fir kriibskrank Kanner
- Action Lions Vaincre le Cancer
- Brain Korea (BK21) PLUS
- [UID/Multi/04423/2019]
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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.
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