ArticleJournal of cancer research and clinical oncology2011
The roles of bioactive sphingolipids in resveratrol-induced apoptosis in HL60: acute myeloid leukemia cells.
Article in Journal of cancer research and clinical oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 53 citations in OpenAlex.
- Functional combination of resveratrol and midostaurin induces cytotoxicity to overcome acquired midostaurin resistance in FLT3-ITD expressing acute myeloid leukemia cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- AFB1 Triggers Lipid Metabolism Disorders through the PI3K/Akt Pathway and Mediates Apoptosis Leading to Hepatotoxicity.Foods (Basel, Switzerland) · 2024Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Article
- Resveratrol triggers anti-proliferative and apoptotic effects in FLT3-ITD-positive acute myeloid leukemia cells via inhibiting ceramide catabolism enzymes.Medical oncology (Northwood, London, England) · 2022Article
- Insights on the Effects of Resveratrol and Some of Its Derivatives in Cancer and Autoimmunity: A Molecule with a Dual Activity.Antioxidants (Basel, Switzerland) · 2020Review
- Review
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- Unexpected profile of sphingolipid contents in blood and bone marrow plasma collected from patients diagnosed with acute myeloid leukemia.Lipids in health and disease · 2017Article
- Targeting acute myeloid leukemia stem cell signaling by natural products.Molecular cancer · 2017Review
- Major apoptotic mechanisms and genes involved in apoptosis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Resveratrol: A potential challenger against gastric cancer.World journal of gastroenterology · 2015Review
- Synergic effects of artemisinin and resveratrol in cancer cells.Journal of cancer research and clinical oncology · 2014Article
- Resveratrol stimulates sphingosine-1-phosphate signaling of cathelicidin production.The Journal of investigative dermatology · 2013Article
- Resveratrol downregulates interleukin-6-stimulated sonic hedgehog signaling in human acute myeloid leukemia.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Sphingosine kinase 1 in cancer.Advances in cancer research · 2013Review
- Article
- Cytotoxic effect of natural trans-resveratrol obtained from elicited Vitis vinifera cell cultures on three cancer cell lines.Plant foods for human nutrition (Dordrecht, Netherlands) · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAcute promyelocytic leukemia results from a translocation between 15 and 17 chromosomes that produce PML/RARα fusion protein. PML/RARα inhibits differentiation of myeloid precursor cells at stem cell level. Resveratrol is a phytoalexin that exerts cytotoxic effects on cancer cells. Ceramides have crucial roles in cell growth, proliferation, differentiation, drug resistance, and apoptosis. In this study, we examined the possible cytotoxic effects of resveratrol on acute myeloid leukemia cells and determined the roles of ceramide-metabolizing genes in resveratrol-induced apoptosis, in addition to investigating the possibility of increasing the sensitivity of HL60 cells to resveratrol by manipulating sphingolipids.
methodsCytotoxic effects of resveratrol, C8:ceramide, PDMP, and SK-1 inhibitor were determined by XTT cell proliferation assay. Changes in caspase-3 enzyme activity and mitochondrial membrane potential (MMP) were measured using caspase-3 colorimetric assay and JC-1 MMP detection kit. Expression levels of ceramide-metabolizing genes were examined by RT-PCR.
resultsThe results revealed that manipulations of ceramide metabolism toward generation or accumulation of apoptotic ceramides increased apoptotic effects of resveratrol in HL60 cells, synergistically. More importantly, gene expression analyses revealed that resveratrol-induced apoptosis via increasing expression levels of ceramide-generating genes and decreasing expression levels of antiapoptotic sphingosine kinase-1 and glucosylceramide synthase genes.
conclusionThese results showed for the first time that increasing intracellular levels of ceramides by biochemical approaches has also increased sensitivity of HL60 cells to resveratrol. We also showed that resveratrol induces apoptosis through manipulating ceramide-metabolizing genes that resulted in the accumulation of ceramides in HL60 cells.
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