Resveratrol Targets Sphingolipid Metabolism to Induce Growth Inhibition in FLT3 ITD Acute Myeloid Leukemia †
Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gul University, 38080 Kayseri, Turkey
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Author to whom correspondence should be addressed.
†
Presented at the 3rd International conference on Natural Products for Cancer Prevention and Therapy, Kayseri, Turkey, 18–20 December 2019.
Proceedings 2019, 40(1), 4; https://doi.org/10.3390/proceedings2019040004
Published: 25 December 2019
(This article belongs to the Proceedings of The 3rd International conference on Natural Products for Cancer Prevention and Therapy)
Abstract
:Sphingolipids are important signaling lipids which play crucial roles to determine the cell fate. Ceramide, apoptotic central molecule of sphingolipid metabolism, which is produced through de novo pathway by serine palmitoyl transferase (SPT) and can be converted to antiapoptotic sphingosine-1-phosphate (S1P) and glucosyl ceramide (GC) by sphingosine kinase (SK) and glucosyl ceramide synthase (GCS), respectively. It is aimed to investigate therapeutic potential of resveratrol on FLT3-ITD (Internal Tandem Duplication) AML cells and to identify potential mechanism behind resveratrol-mediated growth inhibition by targeting of ceramide metabolism. The cytotoxic effects of resveratrol, SPT inhibitor (myricoin), SK-1 inhibitor (SKI II), GCS inhibitor (PDMP), resveratrol: SPT inhibitor, resveratrol: SK-1 inhibitor and resveratrol: GCS inhibitor combinations on MOLM-13 and MV4-11 FLT3 ITD AML cells were investigated by cell proliferation assay. Apoptosis was evaluated by annexin V/PI double staining. There were synergistic cytotoxic effects of resveratrol with co-administration of SPT inhibitor, SK-1 inhibitor and GCS inhibitor and apoptosis was synergistically induced for resveratrol and its combinations. This preliminary data showed for the first time that resveratrol might inhibit the growth of FLT3 ITD AML cells through targeting ceramide metabolism.
Acknowledgments
This project is supported by Abdullah Gul University-BAP (Project number: FAB-2016-66).
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MDPI and ACS Style
Ersöz, N.Ş.; Adan, A. Resveratrol Targets Sphingolipid Metabolism to Induce Growth Inhibition in FLT3 ITD Acute Myeloid Leukemia. Proceedings 2019, 40, 4. https://doi.org/10.3390/proceedings2019040004
AMA Style
Ersöz NŞ, Adan A. Resveratrol Targets Sphingolipid Metabolism to Induce Growth Inhibition in FLT3 ITD Acute Myeloid Leukemia. Proceedings. 2019; 40(1):4. https://doi.org/10.3390/proceedings2019040004
Chicago/Turabian StyleErsöz, Nur Şebnem, and Aysun Adan. 2019. "Resveratrol Targets Sphingolipid Metabolism to Induce Growth Inhibition in FLT3 ITD Acute Myeloid Leukemia" Proceedings 40, no. 1: 4. https://doi.org/10.3390/proceedings2019040004
