{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T18:35:14Z","timestamp":1773167714454,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T00:00:00Z","timestamp":1594771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["57440917"],"award-info":[{"award-number":["57440917"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nature is an indispensable source of new drugs, providing unique bioactive lead structures for drug discovery. In the present study, secalonic acid F (SAF), a naturally occurring ergochrome pigment, was studied for its cytotoxicity against various leukemia and multiple myeloma cells by the resazurin assay. SAF exhibited cytotoxic activity on both leukemia and multiple myeloma cells. Generally, multiple myeloma cells were more sensitive to SAF than leukemia cells. NCI-H929 cells were the most affected cells among the tested panel of multiple myeloma cell lines and were taken for further studies to assess the mode of action of SAF on those cells. Cell cycle analysis revealed that SAF induced S and G2\/M arrest in NCI-H929 cells. SAF-associated apoptosis and necrosis resulted in cytotoxicity. SAF further inclined the disassembly of the tubulin network, which may also account for its cytotoxicity. COMPARE and hierarchical cluster analyses of transcriptome-wide expression profiles of the NCI tumor cell line panel identified genes involved in numerous cellular processes (e.g., cell differentiation, cell migration, and other numerous signaling pathways) notably correlated with log10IC50 values for secalonic acid. In conclusion, the present study supports the therapeutic potential of SAF to treat multiple myeloma.<\/jats:p>","DOI":"10.3390\/molecules25143224","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T07:31:28Z","timestamp":1595403088000},"page":"3224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Chemometric and Transcriptomic Profiling, Microtubule Disruption and Cell Death Induction by Secalonic Acid in Tumor Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-8994","authenticated-orcid":false,"given":"Nadire","family":"\u00d6zenver","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey"},{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Dawood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"},{"name":"Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al-Neelain University, Khartoum 11121, Sudan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmond","family":"Fleischer","sequence":"additional","affiliation":[{"name":"MicroCombiChem GmbH, 65203 Wiesbaden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette","family":"Klinger","sequence":"additional","affiliation":[{"name":"MicroCombiChem GmbH, 65203 Wiesbaden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-4050","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmacy and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"ref_1","unstructured":"(2020, May 25). World Health Organization. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1161\/CIRCRESAHA.116.309573","article-title":"The future of onco-cardiology: We are not just \u201cside effect hunters\u201d","volume":"119","author":"Abe","year":"2016","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.fct.2018.11.041","article-title":"Adverse drug reactions of anticancer drugs derived from natural sources","volume":"123","author":"Tewari","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2217\/fca-2016-0081","article-title":"Cardio-oncology: Cardiovascular complications of cancer therapy","volume":"13","author":"Henning","year":"2017","journal-title":"Future Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/S1470-2045(14)70442-5","article-title":"International myeloma working group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ajh.24402","article-title":"Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management","volume":"91","author":"Vincent","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1182\/blood-2007-08-104984","article-title":"Recent major improvement in long-term survival of younger patients with multiple myeloma","volume":"111","author":"Brenner","year":"2008","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s12185-016-2040-0","article-title":"Mechanisms of action and resistance for multiple myeloma novel drug treatments","volume":"104","author":"Lida","year":"2016","journal-title":"Int. J. Hematol."},{"key":"ref_10","first-page":"87","article-title":"Drug targets and resistance mechanisms in multiple myeloma","volume":"1","author":"Nass","year":"2018","journal-title":"Cancer Drug Resist."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/leu.2013.313","article-title":"Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients","volume":"28","author":"Kumar","year":"2014","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000447076","article-title":"Leukemia","volume":"43","author":"Juliusson","year":"2016","journal-title":"Prog. Tumor. Res."},{"key":"ref_13","unstructured":"(2020, June 27). National Cancer Institute, Available online: https:\/\/www.cancer.gov\/types\/leukemia."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: A comprehensive review and 2017 update","volume":"7","author":"Terwilliger","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1002\/cncr.29383","article-title":"New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia","volume":"121","author":"Jabbour","year":"2015","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1182\/blood-2009-07-235358","article-title":"Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the European LeukemiaNet","volume":"115","author":"Estey","year":"2010","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural products as sources of new drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1248\/cpb.19.199","article-title":"The isolation of secalonic acid A from Aspergillus ochraceus cultured on rice","volume":"19","author":"Yamazaki","year":"1971","journal-title":"Chem. Pharm. Bull."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1021\/jo00422a042","article-title":"Secalonic acids D and F are toxic metabolites of Aspergillus aculeatus","volume":"42","author":"Andersen","year":"1977","journal-title":"J. Org. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0048-3575(89)90166-1","article-title":"Tricyclazole as an inhibitor of polyketide metabolism in the onion pink root rot pathogen, Pyrenochaeta terrestris","volume":"34","author":"Lazarovits","year":"1989","journal-title":"Pestic. Biochem. Phys."},{"key":"ref_21","unstructured":"Luisa, B.G. (2012). Handbook of Toxic Fungal Metabolites, Elsevier."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0040-4020(70)85006-2","article-title":"The isolation, structure and absolute configuration of secalonic acid D, the toxic metabolite of Penicillium oxalicum","volume":"26","author":"Steyn","year":"1970","journal-title":"Tetrahedron"},{"key":"ref_23","unstructured":"Betina, V. (1984). Mycotoxins: Production, Isolation, Separation, and Purification, Elsevier. [8th ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4913","DOI":"10.1002\/chem.200800035","article-title":"New mono- and dimeric members of the secalonic acid family: Blennolides\u2005A\u2013G isolated from the fungus Blennoria sp.","volume":"14","author":"Zhang","year":"2008","journal-title":"Chemistry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/mrc.2035","article-title":"1H and 13C NMR signal assignments of paecilin A and B, two new chromone derivatives from mangrove endophytic fungus Paecilomyces sp. (tree 1\u20137)","volume":"45","author":"Guo","year":"2007","journal-title":"Magn. Reson. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1158\/0008-5472.CAN-14-2312","article-title":"Secalonic acid-d represses hif1\u03b1\/vegf-mediated angiogenesis by regulating the Akt\/mTOR\/p70S6K signaling cascade","volume":"75","author":"Guru","year":"2015","journal-title":"Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1248\/cpb.22.1600","article-title":"Phlogistic activity of secalonic acid A","volume":"22","author":"Harada","year":"1974","journal-title":"Chem. Pharm. Bull"},{"key":"ref_28","first-page":"900","article-title":"5-di-(2\u2032-tetrahydropyranyl)secalonic acid D as a new antibiotic derivative with anticancer activity","volume":"71","author":"Iwaguchi","year":"1980","journal-title":"GANN"},{"key":"ref_29","first-page":"339","article-title":"Cytostatic activity of naturally isolated isomers of secalonic acids and their chemically rearranged dimers","volume":"13","author":"Kurobane","year":"1987","journal-title":"Drugs Exp. Clin. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/BF00254193","article-title":"Mechanism of the antitumor activity of 5,5\u2032-bis(2\u2032-tetrahydropyranyl) secalonic acid D against Meth-A","volume":"11","author":"Shimizu","year":"1983","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_31","first-page":"864","article-title":"Cytotoxicity of the secondary metabolites of marine mangrove fungus Paecilomyces sp. tree 1-7 on human hepatoma cell line HepG2","volume":"31","author":"Cai","year":"2008","journal-title":"Zhong Yao Cai"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"796","DOI":"10.3109\/13880209.2010.548817","article-title":"Secalonic acid D as a novel DNA topoisomerase I inhibitor from marine lichen-derived fungus Gliocladium sp. T31","volume":"49","author":"Hong","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/BF02977469","article-title":"Secalonic acid D.; A cytotoxic constituent from marine lichen-derived fungus Gliocladium sp. T31","volume":"29","author":"Ren","year":"2006","journal-title":"Arch. Pharm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s11418-020-01390-0","article-title":"Secalonic acid D as a selective cytotoxic substance on the cancer cells adapted to nutrient starvation","volume":"74","author":"Tang","year":"2020","journal-title":"J. Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.bcp.2013.04.003","article-title":"Secalonic acid D reduced the percentage of side populations by down-regulating the expression of ABCG2","volume":"85","author":"Hu","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_36","first-page":"387","article-title":"The cell toxicity effect of secalonic acid D on GH3 cells and the related mechanisms","volume":"23","author":"Liao","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.4161\/cc.8.15.9170","article-title":"Secalonic acid D induced leukemia cell apoptosis and cell cycle arrest of G(1) with involvement of GSK-3beta\/beta-catenin\/c-Myc pathway","volume":"8","author":"Zhang","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.apsb.2018.12.006","article-title":"Secalonic acid D induces cell apoptosis in both sensitive and ABCG2-overexpressing multidrug resistant cancer cells through upregulating c-Jun expression","volume":"9","author":"Zhang","year":"2019","journal-title":"Acta Pharm. Sin. B."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.3390\/md13042010","article-title":"Marine natural products as breast cancer resistance protein inhibitors","volume":"13","author":"Cherigo","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0040-4020(01)98303-6","article-title":"Mould metabolites\u2014IV: The isolation and constitution of some ergot pigments","volume":"21","author":"Aberhart","year":"1965","journal-title":"Tetrahedron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2134\/agronj2001.93160x","article-title":"Allelopathy of Aspergillus japonicus on crops","volume":"93","author":"Zeng","year":"2001","journal-title":"Agron. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"72","DOI":"10.2134\/agronj2001.93172x","article-title":"Physiological and biochemical mechanism of allelopathy of secalonic acid F on higher plants","volume":"93","author":"Zeng","year":"2001","journal-title":"Agron. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"344","DOI":"10.4149\/neo_2017_304","article-title":"Secalonic acid- F inhibited cell growth more effectively than 5-fluorouracil on hepatocellular carcinoma in vitro and in vivo","volume":"64","author":"Gao","year":"2017","journal-title":"Neoplasma"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Xie, L., Li, M., Liu, D., Wang, X., Wang, P., Dai, H., Yang, W., Liu, W., Hu, X., and Zhao, M. (2019). Secalonic acid-F, a novel mycotoxin, represses the progression of hepatocellular carcinoma via MARCH1 regulation of the PI3K\/AKT\/\u03b2-catenin signaling pathway. Molecules, 24.","DOI":"10.3390\/molecules24030393"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3892\/or.2012.2062","article-title":"Differential proteomic analysis of HL60 cells treated with secalonic acid F reveals caspase 3-induced cleavage of Rho GDP dissociation inhibitor 2","volume":"28","author":"Li","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1080\/15287397909529821","article-title":"Toxicity of secalonic acid D","volume":"5","author":"Reddy","year":"1979","journal-title":"J. Toxicol. Environ. Health"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/73432","article-title":"Systematic variation in gene expression patterns in human cancer cell lines","volume":"24","author":"Ross","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/73439","article-title":"A gene expression database for the molecular pharmacology of cancer","volume":"24","author":"Scherf","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1126\/science.282.5389.627g","article-title":"Fishing expeditions","volume":"282","author":"Weinstein","year":"1998","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3253","article-title":"Microtubule-binding agents: A dynamic field of cancer therapeutics","volume":"9","author":"Dumontet","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc1317","article-title":"Microtubules as a target for anticancer drugs","volume":"4","author":"Jordan","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1097\/FPC.0b013e3283335277","article-title":"Taxane pathway","volume":"19","author":"Oshiro","year":"2009","journal-title":"Pharmacogenet. Genom."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.semcdb.2011.09.017","article-title":"Regulation of cell migration by dynamic microtubules","volume":"22","author":"Kaverina","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_54","first-page":"589","article-title":"Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay","volume":"48","author":"Alley","year":"1988","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1093\/jnci\/82.13.1113","article-title":"Comparison of in vitro anticancer-drug-screening data generated with a tetrazolium assay versus a protein assay against a diverse panel of human tumor cell lines","volume":"82","author":"Rubinstein","year":"1990","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.phymed.2016.04.007","article-title":"Cytotoxicity of seven naturally occurring phenolic compounds towards multi-factorial drug-resistant cancer cells","volume":"23","author":"Kuete","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1046\/j.1432-1327.2000.01606.x","article-title":"Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity","volume":"267","author":"Wilson","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3389\/fphar.2018.00136","article-title":"Molecular determinants of sensitivity or resistance of cancer cells toward sanguinarine","volume":"9","author":"Saeed","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1093\/jnci\/81.14.1088","article-title":"Display and analysis of patterns of differential activity of drugs against human tumor cell lines: Development of mean graph and COMPARE algorithm","volume":"81","author":"Paull","year":"1989","journal-title":"J. Natl. Cancer Inst."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3224\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:48:40Z","timestamp":1760176120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/14\/3224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,15]]},"references-count":59,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["molecules25143224"],"URL":"https:\/\/doi.org\/10.3390\/molecules25143224","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,15]]}}}