{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:34:23Z","timestamp":1790112863968,"version":"4.0.1"},"reference-count":100,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Gda\u0144sk (Gda\u0144sk, Poland) and Polish Ministry of Science and Higher Education","award":["MN grant no. 01-0173\/08\/280"],"award-info":[{"award-number":["MN grant no. 01-0173\/08\/280"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute myeloid leukemia is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Despite recent advances in the treatment of this disease, the prognosis and overall long-term survival for patients remain poor, which drives the search for new chemotherapeutics and treatment strategies. Piceatannol, a polyphenolic compound present in grapes and wine, appears to be a promising chemotherapeutic agent in the treatment of leukemia. The aim of the present study was to examine whether piceatannol induces autophagy and\/or apoptosis in HL-60 human acute myeloid leukemia cells and whether HL-60 cells are able to acquire resistance to piceatannol toxicity. We found that piceatannol at the IC90 concentration of 14 \u00b5M did not induce autophagy in HL-60 cells. However, it induced caspase-dependent apoptosis characterized by phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. Our findings also imply that HL-60 cells are able to acquire resistance to piceatannol toxicity via mechanisms related to MRP1 activity. Our results suggest that the use of piceatannol as a potential chemotherapeutic agent may be associated with the risk of multidrug resistance, warranting its use in combination with other chemotherapeutic agents.<\/jats:p>","DOI":"10.3390\/ijms221910597","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T10:22:42Z","timestamp":1632997362000},"page":"10597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Piceatannol, a Structural Analog of Resveratrol, Is an Apoptosis Inducer and a Multidrug Resistance Modulator in HL-60 Human Acute Myeloid Leukemia Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-0799","authenticated-orcid":false,"given":"Kamila","family":"Siedlecka-Kroplewska","sequence":"first","affiliation":[{"name":"Department of Histology, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1792-8975","authenticated-orcid":false,"given":"Agata","family":"Wro\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Histology, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-8166","authenticated-orcid":false,"given":"Zbigniew","family":"Kmie\u0107","sequence":"additional","affiliation":[{"name":"Department of Histology, Medical University of Gda\u0144sk, 80-211 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1242\/dmm.015974","article-title":"Acute myeloid leukaemia: A paradigm for the clonal evolution of cancer?","volume":"7","author":"Grove","year":"2014","journal-title":"Dis. Models Mech."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s12098-015-1695-5","article-title":"Leukemias in Children","volume":"82","author":"Seth","year":"2015","journal-title":"Indian J. Pediatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e441","DOI":"10.1038\/bcj.2016.50","article-title":"Acute myeloid leukemia: A comprehensive review and 2016 update","volume":"6","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.annonc.2020.02.018","article-title":"Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Heuser","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/BS9.0000000000000015","article-title":"Tumor heterogeneity of acute myeloid leukemia: Insights from single-cell sequencing","volume":"1","author":"Chen","year":"2019","journal-title":"Blood Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/MOP.0000000000000855","article-title":"Pediatric acute myeloid leukemia: Updates on biology, risk stratification, and therapy","volume":"32","author":"Elgarten","year":"2020","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_7","first-page":"38","article-title":"Acute Myeloid Leukemia: A Review","volume":"103","author":"Pelcovits","year":"2020","journal-title":"R. I. Med. J. (2013)"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1038\/s41375-021-01218-0","article-title":"Hypomethylating agents (HMA) for the treatment of acute myeloid leukemia and myelodysplastic syndromes: Mechanisms of resistance and novel HMA-based therapies","volume":"35","author":"Stomper","year":"2021","journal-title":"leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/ijlh.13241","article-title":"P-glycoprotein and multidrug resistance-associated protein-1 expression in acute myeloid leukemia: Biological and prognosis implications","volume":"42","author":"Soares","year":"2020","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103281","DOI":"10.1016\/j.critrevonc.2021.103281","article-title":"Update on drug transporter proteins in acute myeloid leukemia: Pathological implication and clinical setting","volume":"160","author":"Vasconcelos","year":"2021","journal-title":"Crit. Rev. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41568-018-0005-8","article-title":"Revisiting the role of ABC transporters in multidrug-resistant cancer","volume":"18","author":"Robey","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/1479-7364-3-3-281","article-title":"Human ATP-binding cassette (ABC) transporter family","volume":"3","author":"Vasiliou","year":"2008","journal-title":"Hum. Genom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/jebm.12434","article-title":"ATP-binding cassette (ABC) transporters in cancer: A review of recent updates","volume":"14","author":"Wang","year":"2021","journal-title":"J. Evidence-Based Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"793","DOI":"10.2174\/138161282005140214165212","article-title":"ABC Transporters in Multidrug Resistance and Pharmacokinetics, and Strategies for Drug Development","volume":"20","author":"Choi","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1177\/38.9.1974900","article-title":"Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues","volume":"38","author":"Boccia","year":"1990","journal-title":"J. Histochem. Cytochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15665","DOI":"10.1073\/pnas.95.26.15665","article-title":"A multidrug resistance transporter from human MCF-7 breast cancer cells","volume":"95","author":"Doyle","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/clpt.2013.175","article-title":"Profiling Solute Carrier Transporters in the Human Blood\u2013Brain Barrier","volume":"94","author":"Geier","year":"2013","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_18","first-page":"2163","article-title":"Expression of the multidrug resistance-associated protein (MRP) in acute leukaemia","volume":"8","author":"Hart","year":"1994","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1182\/blood.V96.1.365","article-title":"Expression of breast cancer resistance protein in blast cells from patients with acute leukemia","volume":"96","author":"Ross","year":"2000","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1002\/1873-3468.13966","article-title":"Structures of ABC transporters: Handle with care","volume":"594","author":"Lewinson","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.2174\/0929867324666171012105143","article-title":"ATP-binding Cassette Exporters: Structure and Mechanism with a Focus on P-glycoprotein and MRP1","volume":"26","author":"Arana","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Xing, J., Huang, S., Heng, Y., Mei, H., and Pan, X. (2020). Computational Insights into Allosteric Conformational Modulation of P-Glycoprotein by Substrate and Inhibitor Binding. Molecules, 25.","DOI":"10.3390\/molecules25246006"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1016\/j.xphs.2017.04.022","article-title":"A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics","volume":"106","author":"Saaby","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"406","DOI":"10.3109\/03602532.2015.1105253","article-title":"MRP1 and its role in anticancer drug resistance","volume":"47","author":"Lu","year":"2015","journal-title":"Drug Metab. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-pharmtox-011613-135959","article-title":"Targeting Multidrug Resistance Protein 1 (MRP1,ABCC1): Past, Present, and Future","volume":"54","author":"Cole","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/17425255.2019.1591373","article-title":"ABCG2\/BCRP: Variants, transporter interaction profile of substrates and inhibitors","volume":"15","author":"Safar","year":"2019","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.bcp.2017.10.004","article-title":"BCRP\/ABCG2 and high-alert medications: Biochemical, pharmacokinetic, pharmacogenetic, and clinical implications","volume":"147","author":"Hira","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1182\/blood.V78.3.586.586","article-title":"Multidrug resistance (mdr1) gene expression in adult acute leukemias: Correlations with treatment outcome and in vitro drug sensitivity","volume":"78","author":"Marie","year":"1991","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/sj.leu.2404692","article-title":"ABC transporters and drug resistance in leukemia: Was P-gp nothing but the first head of the Hydra?","volume":"21","author":"Steinbach","year":"2007","journal-title":"Leukemia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1182\/blood.V91.12.4480","article-title":"Pgp and MRP activities using calcein-AM are prognostic factors in adult acute myeloid leukemia patients","volume":"91","author":"Legrand","year":"1998","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1182\/blood.V82.10.3157.3157","article-title":"Predominance of functional multidrug resistance (MDR-1) phenotype in CD34+ acute myeloid leukemia cells","volume":"82","author":"Schoester","year":"1993","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/sj.leu.2402541","article-title":"BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia","volume":"16","author":"Steinbach","year":"2002","journal-title":"Leukemia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.3324\/haematol.2010.031823","article-title":"ATP Binding Cassette transporters associated with chemoresistance: Transcriptional profiling in extreme cohorts and their prognostic impact in a cohort of 281 acute myeloid leukemia patients","volume":"96","author":"Marzac","year":"2011","journal-title":"Haematologica"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11112","DOI":"10.1021\/jf102650d","article-title":"Extract of Passion Fruit (Passiflora edulis) Seed Containing High Amounts of Piceatannol Inhibits Melanogenesis and Promotes Collagen Synthesis","volume":"58","author":"Matsui","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4713","DOI":"10.1021\/jf040095e","article-title":"Resveratrol, Pterostilbene, and Piceatannol in Vaccinium Berries","volume":"52","author":"Rimando","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.chroma.2008.12.058","article-title":"Solid-phase microextraction on-fiber derivatization for the analysis of some polyphenols in wine and grapes using gas chromatography\u2013mass spectrometry","volume":"1216","author":"Campillo","year":"2009","journal-title":"J. Chromatogr. A"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1021\/jf020939z","article-title":"Postharvest UV-C-Irradiated Grapes as a Potential Source for Producing Stilbene-Enriched Red Wines","volume":"51","author":"Espin","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1755-5949.2008.00074.x","article-title":"Comparative Neuroprotective Properties of Stilbene and Catechin Analogs: Action Via a Plasma Membrane Receptor Site?","volume":"15","author":"Bastianetto","year":"2009","journal-title":"CNS Neurosci. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1093\/jac\/dkm099","article-title":"Resveratrol inhibition of Propionibacterium acnes","volume":"59","author":"Docherty","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S0891-5849(01)00474-9","article-title":"Beneficial effects of astringinin, a resveratrol analogue, on the ischemia and reperfusion damage in rat heart","volume":"30","author":"Hung","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00011-014-0777-6","article-title":"Piceatannol inhibits phorbol ester-induced expression of COX-2 and iNOS in HR-1 hairless mouse skin by blocking the activation of NF-\u03baB and AP-1","volume":"63","author":"Liu","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1677\/jme.1.01783","article-title":"The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor \u03b1 in human breast cancer cells","volume":"35","author":"Maggiolini","year":"2005","journal-title":"J. Mol. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.bbrc.2012.05.017","article-title":"Piceatannol, a resveratrol derivative, promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and suppresses blood glucose levels in type 2 diabetic model db\/db mice","volume":"422","author":"Minakawa","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.bcp.2004.12.001","article-title":"Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: Structure\u2013activity relationship","volume":"69","author":"Murias","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","first-page":"2055","article-title":"Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids","volume":"25","author":"Chowdhury","year":"2005","journal-title":"Anticancer. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5402\/2012\/272697","article-title":"AKT\/mTOR as Novel Targets of Polyphenol Piceatannol Possibly Contributing to Inhibition of Proliferation of Cultured Prostate Cancer Cells","volume":"2012","author":"Hsieh","year":"2012","journal-title":"ISRN Urol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.tiv.2010.12.006","article-title":"Piceatannol enhances TRAIL-induced apoptosis in human leukemia THP-1 cells through Sp1- and ERK-dependent DR5 up-regulation","volume":"25","author":"Kang","year":"2011","journal-title":"Toxicol. Vitr."},{"key":"ref_48","first-page":"961","article-title":"Induction of apoptosis by piceatannol in human leukemic U937 cells through down-regulation of Bcl-2 and activation of caspases","volume":"19","author":"Kim","year":"2008","journal-title":"Oncol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/j.biocel.2005.03.004","article-title":"Pterostilbene and 3\u2032-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells","volume":"37","author":"Tolomeo","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/mnfr.200700252","article-title":"The grape and wine constituent piceatannol inhibits proliferation of human bladder cancer cells via blocking cell cycle progression and inducing Fas\/membrane bound Fas ligand-mediated apoptotic pathway","volume":"52","author":"Kuo","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00394-004-0471-5","article-title":"The grape and wine polyphenol piceatannol is a potent inducer of apoptosis in human SK-Mel-28 melanoma cells","volume":"43","author":"Larrosa","year":"2004","journal-title":"Eur. J. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.canlet.2009.05.011","article-title":"Piceatannol, a natural stilbene from grapes, induces G1 cell cycle arrest in androgen-insensitive DU145 human prostate cancer cells via the inhibition of CDK activity","volume":"285","author":"Lee","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.biocel.2010.05.007","article-title":"Piceatannol induces Fas and FasL up-regulation in human leukemia U937 cells via Ca2+\/p38\u03b1 MAPK-mediated activation of c-Jun and ATF-2 pathways","volume":"42","author":"Liu","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/jat.1725","article-title":"Selective apoptotic effects of piceatannol and myricetin in human cancer cells","volume":"32","author":"Morales","year":"2012","journal-title":"J. Appl. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1093\/carcin\/bgp199","article-title":"Pro- and anticarcinogenic mechanisms of piceatannol are activated dose dependently in MCF-7 breast cancer cells","volume":"31","author":"Vo","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/sj.leu.2402284","article-title":"Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts","volume":"15","author":"Wieder","year":"2001","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/jn\/132.2.298","article-title":"Piceatannol, a Natural Analog of Resveratrol, Inhibits Progression through the S Phase of the Cell Cycle in Colorectal Cancer Cell Lines","volume":"132","author":"Wolter","year":"2002","journal-title":"J. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.bbrc.2014.08.150","article-title":"Piceatannol promotes apoptosis via up-regulation of microRNA-129 expression in colorectal cancer cell lines","volume":"452","author":"Zhang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.tiv.2019.03.040","article-title":"Induction of autophagy, apoptosis and aquisition of resistance in response to piceatannol toxicity in MOLT-4 human leukemia cells","volume":"59","year":"2019","journal-title":"Toxicol. Vitr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3851","DOI":"10.4161\/cc.22027","article-title":"Pro-autophagic polyphenols reduce the acetylation of cytoplasmic proteins","volume":"11","author":"Pietrocola","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1080\/01635581.2019.1578387","article-title":"Involvement of the PI3K\/Akt\/Nrf2 Signaling Pathway in Resveratrol-Mediated Reversal of Drug Resistance in HL-60\/ADR Cells","volume":"71","author":"Li","year":"2019","journal-title":"Nutr. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.3892\/etm.2014.1662","article-title":"Resveratrol reverses multidrug resistance in human breast cancer doxorubicin-resistant cells","volume":"7","author":"Huang","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_63","first-page":"5825","article-title":"Expression of genes and proteins of multidrug resistance in gastric cancer cells treated with resveratrol","volume":"15","author":"Mieszala","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1182\/blood.V70.5.1233.1233","article-title":"The HL-60 promyelocytic leukemia cell line: Proliferation, differentiation, and cellular oncogene expression","volume":"70","author":"Collins","year":"1987","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/0145-2126(95)00036-N","article-title":"Leukemia cell lines: In vitro models for the study of acute promyelocytic leukemia","volume":"19","author":"Drexler","year":"1995","journal-title":"Leuk. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.2174\/0929867322666150209150639","article-title":"A simple and reliable approach for assessing anticancer activity in vitro","volume":"22","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/auto.1.1.1270","article-title":"Maturation of Autophagic Vacuoles in Mammalian Cells","volume":"1","author":"Eskelinen","year":"2005","journal-title":"Autophagy"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","article-title":"LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing","volume":"19","author":"Kabeya","year":"2000","journal-title":"EMBO J."},{"key":"ref_69","first-page":"3010","article-title":"Methods to detect P-glycoprotein-associated multidrug resistance in patients\u2019 tumors: Consensus recommendations","volume":"56","author":"Beck","year":"1996","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/(SICI)1097-0320(19981215)34:6<248::AID-CYTO2>3.0.CO;2-X","article-title":"Reference method for detection of Pgp mediated multidrug resistance in human hematological malignancies: A method validated by the laboratories of the French Drug Resistance Network","volume":"34","author":"Huet","year":"1998","journal-title":"Cytometry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1365-2141.1992.tb04608.x","article-title":"Detection of activity of P-glycoprotein in human tumour samples using rhodamine 123","volume":"82","author":"Ludescher","year":"1992","journal-title":"Br. J. Haematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15344","DOI":"10.1021\/bi0020574","article-title":"Rhodamine 123 Binds to Multiple Sites in the Multidrug Resistance Protein (MRP1)","volume":"39","author":"Daoud","year":"2000","journal-title":"Biochemistry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/0959-8049(94)90187-2","article-title":"A comparison of rhodamine 123 accumulation and efflux in cells with P-glycoprotein-mediated and MRP-associated multidrug resistance phenotypes","volume":"30","author":"Twentyman","year":"1994","journal-title":"Eur. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1158\/1078-0432.CCR-04-1725","article-title":"Cyclosporin A Is a Broad-Spectrum Multidrug Resistance Modulator","volume":"11","author":"Qadir","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"27807","DOI":"10.1016\/S0021-9258(18)46856-1","article-title":"The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates","volume":"269","author":"Leier","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_76","first-page":"6635","article-title":"Acquired mutations in the MXR\/BCRP\/ABCP gene alter substrate specificity in MXR\/BCRP\/ABCP-overexpressing cells","volume":"61","author":"Honjo","year":"2001","journal-title":"Cancer Res."},{"key":"ref_77","first-page":"417","article-title":"Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C","volume":"1","author":"Allen","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1110\/ps.051998406","article-title":"The nature of amino acid 482 of human ABCG2 affects substrate transport and ATP hydrolysis but not substrate binding","volume":"15","author":"Ejendal","year":"2006","journal-title":"Protein Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"26059","DOI":"10.1074\/jbc.M803230200","article-title":"Interaction with the 5D3 Monoclonal Antibody Is Regulated by Intramolecular Rearrangements but Not by Covalent Dimer Formation of the Human ABCG2 Multidrug Transporter","volume":"283","author":"Litman","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1248\/bpb.30.2007","article-title":"Piceatannol Inhibits Melanogenesis by Its Antioxidative Actions","volume":"30","author":"Yokozawa","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"574","DOI":"10.5603\/FHC.2012.0080","article-title":"Pterostilbene induces cell cycle arrest and apoptosis in MOLT4 human leukemia cells","volume":"50","author":"Jozwik","year":"2012","journal-title":"Folia Histochem. Et Cytobiol."},{"key":"ref_82","first-page":"545","article-title":"Pterostilbene induces accumulation of autophagic vacuoles followed by cell death in HL60 human leukemia cells","volume":"64","author":"Jozwik","year":"2013","journal-title":"J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc."},{"key":"ref_83","first-page":"825","article-title":"The wine polyphenol resveratrol modulates autophagy and induces apoptosis in MOLT-4 and HL-60 human leukemia cells","volume":"70","author":"Wozniak","year":"2020","journal-title":"J Physiol Pharmacol"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1172\/JCI20039","article-title":"Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene","volume":"112","author":"Qu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"15077","DOI":"10.1073\/pnas.2436255100","article-title":"Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor","volume":"100","author":"Yue","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1158\/1078-0432.CCR-10-2372","article-title":"Measurements of Tumor Cell Autophagy Predict Invasiveness, Resistance to Chemotherapy, and Survival in Melanoma","volume":"17","author":"Ma","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1038\/cddis.2010.67","article-title":"Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells","volume":"1","author":"Marino","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Musial, C., Siedlecka-Kroplewska, K., Kmiec, Z., and Gorska-Ponikowska, M. (2021). Modulation of Autophagy in Cancer Cells by Dietary Polyphenols. Antioxidants, 10.","DOI":"10.3390\/antiox10010123"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Lang, F., Qin, Z., Li, F., Zhang, H., Fang, Z., and Hao, E. (2015). Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells. PLOS ONE, 10.","DOI":"10.1371\/journal.pone.0129196"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.canlet.2013.03.023","article-title":"Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma","volume":"336","author":"Tang","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1080\/1042819032000159861","article-title":"Problems Related to Resistance to Cytarabine in Acute Myeloid Leukemia","volume":"45","author":"Cros","year":"2004","journal-title":"Leuk. Lymphoma"},{"key":"ref_92","first-page":"1255","article-title":"Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL-60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells","volume":"15","author":"Chen","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/10245330701562535","article-title":"Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance","volume":"12","author":"Baran","year":"2007","journal-title":"Hematology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"109885","DOI":"10.1016\/j.biopha.2020.109885","article-title":"Grape seed proanthocyanidin extract reverses multidrug resistance in HL-60\/ADR cells via inhibition of the PI3K\/Akt signaling pathway","volume":"125","author":"Lin","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_95","first-page":"163","article-title":"Determination of P-glycoprotein, MDR-related protein 1, breast cancer resistance protein, and lung-resistance protein expression in leukemic stem cells of acute myeloid leukemia","volume":"74","author":"Oliveira","year":"2008","journal-title":"Cytom. Part B Clin. Cytom."},{"key":"ref_96","first-page":"4127","article-title":"Inhibition of MRP1 transport activity by phenolic and terpenic compounds isolated from Euphorbia species","volume":"27","author":"Wesolowska","year":"2008","journal-title":"Anticancer. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.bcp.2006.07.035","article-title":"Induction of G2\/M phase arrest and apoptosis of human leukemia cells by potent antitumor triazoloacridinone C-1305","volume":"72","author":"Augustin","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"448","DOI":"10.4049\/jimmunol.125.1.448","article-title":"Fc receptors of a human promyelocytic leukemic cell line: Evidence for two types of receptors defined by binding of the staphylococcal protein A-IgG1 complex","volume":"125","author":"Crabtree","year":"1980","journal-title":"J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/cyto.a.22995","article-title":"Elimination of erroneous results in flow cytometry caused by antibody binding to Fc receptors on human monocytes and macrophages","volume":"89","author":"Andersen","year":"2016","journal-title":"Cytom. Part A"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/cyto.a.20333","article-title":"Flow cytometry controls, instrument setup, and the determination of positivity","volume":"69A","author":"Maecker","year":"2006","journal-title":"Cytom. 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