{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:26:48Z","timestamp":1767338808420,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Research Council of Turkey (TUBITAK)","award":["1919B012212473"],"award-info":[{"award-number":["1919B012212473"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cancer is a common disease worldwide, and medicinal plants are widely used for its treatment. A. agallocha is a plant from the Thymelaeaceae family that is endemic to East Asia. Popularly known as the agar tree, this plant is used in the treatment of heart diseases, asthma, cough, ulcers, gout, inflammation, and pain. In this study, the cytotoxic, apoptotic\/necrotic, and antioxidant activities of root extracts of A. agallocha and their effects on gene expression were investigated. Cytotoxic effects were analyzed by the MTT assay method, apoptotic\/necrotic effects by the double staining method, and antioxidant effects by the DPPH radical scavenging assay. According to the results, the best cytotoxic effect in HepG2 cells was observed at 1000 \u00b5g\/mL hexane extract. In MCF-7 cells, 250 \u00b5g\/mL hexane extract showed the best activity. Antioxidant activity was highest in dH2O and lowest in the methanol extract. In gene expression analysis, hexane and methanol extracts decreased p53 expression in HepG2 cells, while acetone extract increased it. In addition, the expression of Bax and Bcl-2 genes generally increased. This study revealed the potent cytotoxic, antioxidant, and apoptotic effects of the A. agallocha extract.<\/jats:p>","DOI":"10.3390\/life15040651","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:05:31Z","timestamp":1744776331000},"page":"651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigation of Cytotoxic, Antioxidant, Apoptotic\/Necrotic Activity of Aquilaria agallocha Root Extract and Determination of Gene Expression Levels in HepG2, MCF-7 Cancer Cell Lines"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6892-247X","authenticated-orcid":false,"given":"Semih","family":"Dalk\u0131l\u0131\u00e7","sequence":"first","affiliation":[{"name":"Department of Biology and Molecular Biology and Genetics Program, Faculty of Science, F\u0131rat University, 23119 Elaz\u0131\u011f, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00fctfiye","family":"Kad\u0131o\u011flu Dalk\u0131l\u0131\u00e7","sequence":"additional","affiliation":[{"name":"Department of Biology and Molecular Biology and Genetics Program, Faculty of Science, F\u0131rat University, 23119 Elaz\u0131\u011f, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elgun","family":"\u0130sbenov","sequence":"additional","affiliation":[{"name":"Department of Biology and Molecular Biology and Genetics Program, Faculty of Science, F\u0131rat University, 23119 Elaz\u0131\u011f, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-2703","authenticated-orcid":false,"given":"L\u00fctf\u00fc","family":"Uygur","sequence":"additional","affiliation":[{"name":"Department of Biology and Molecular Biology and Genetics Program, Faculty of Science, F\u0131rat University, 23119 Elaz\u0131\u011f, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ceydanur","family":"Ta\u015fdemir","sequence":"additional","affiliation":[{"name":"Department of Biology and Molecular Biology and Genetics Program, Faculty of Science, F\u0131rat University, 23119 Elaz\u0131\u011f, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Kanser Biyokimyas\u0131","volume":"1","year":"2012","journal-title":"Dicle \u00dcniversitesi Vet. Fak\u00fcltesi Derg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.canlet.2016.04.017","article-title":"The potential role of boswellic acids in cancer prevention and treatment","volume":"377","author":"Roy","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_3","first-page":"211","article-title":"Kemoterapi Alan Kanser Hastalar\u0131nda G\u00f6r\u00fclen Semptomlar ve Tamamlay\u0131c\u0131 Terapi Uygulamalar\u0131 Kullan\u0131mlar\u0131","volume":"9","author":"Purut","year":"2022","journal-title":"Sa\u011fl\u0131k Akad. Derg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"583","DOI":"10.5152\/hsp.2019.440012","article-title":"Meme Kanserinde G\u00fcncel Geli\u015fmeler","volume":"6","author":"Akyolcu","year":"2019","journal-title":"Sa\u011fl\u0131k Bilim. Ve Meslekleri Derg."},{"key":"ref_5","first-page":"72","article-title":"MEME KANSER\u0130NDE KORUNMA","volume":"10","year":"2010","journal-title":"J. Anatolia Nurs. Health Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"24411","DOI":"10.1007\/s11356-021-17795-7","article-title":"Anticancer properties of medicinal plants and their bioactive compounds against breast cancer: A review on recent investigations","volume":"29","author":"Khan","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Thun, M.J., Linet, M.S., Cerhan, J.R., Haiman, C.A., and Schottenfeld, D. (2018). Liver Cancer. Cancer Epidemiology and Prevention, Oxford University Press. [4th ed.].","DOI":"10.1093\/oso\/9780190238667.001.0001"},{"key":"ref_8","first-page":"1465","article-title":"Photochemical activation of drugs for the treatment of therapy-resistant cancers","volume":"14","author":"Weyergang","year":"2015","journal-title":"Photochem. Photobiol. Sci. Off. J. Eur. Photochem. Assoc. Eur. Soc. Photobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S317","DOI":"10.1016\/j.pmrj.2017.05.010","article-title":"The Underutilization of Rehabilitation to Treat Physical Impairments in Breast Cancer Survivors","volume":"9","author":"Stubblefield","year":"2017","journal-title":"PM R"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"St\u00f6cker, A., Mehnert-Theuerkauf, A., Hinz, A., and Ernst, J. (2023). Utilization of complementary and alternative medicine (CAM) by women with breast cancer or gynecological cancer. PloS One, 18.","DOI":"10.1371\/journal.pone.0285718"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ramawat, K.G., and Merillon, J.M. (2008). The Indian Herbal Drugs Scenario in Global Perspectives. Bioactive Molecules and Medicinal Plants, Springer.","DOI":"10.1007\/978-3-540-74603-4"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Korinek, M., Wagh, V.D., Lo, I.-W., Hsu, Y.-M., Hsu, H.-Y., Hwang, T.-L., Wu, Y.-C., Cheng, Y.-B., Chen, B.-H., and Chang, F.-R. (2016). Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17030398"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ismail, S.N., Maulidiani, M., Akhtar, M.T., Abas, F., Ismail, I.S., Khatib, A., Ali, N.A.M., and Shaari, K. (2017). Discriminative Analysis of Different Grades of Gaharu (Aquilaria malaccensis Lamk.) via 1H-NMR-Based Metabolomics Using PLS-DA and Random Forests Classification Models. Mol. Basel Switz., 22.","DOI":"10.3390\/molecules22101612"},{"key":"ref_14","first-page":"89","article-title":"Antitrypanosomal screening and cytotoxic effects of selected medicinal plants","volume":"31","author":"Dyary","year":"2014","journal-title":"Trop. Biomed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5950","DOI":"10.1002\/slct.201700601","article-title":"Bioinspired Green and Facile Fabrication of Au@Ag@AgCl Hybrid Nanoparticles and Their Catalytic and Antimicrobial Properties","volume":"2","author":"Devi","year":"2017","journal-title":"ChemistrySelect"},{"key":"ref_16","first-page":"32","article-title":"Phytochemicals: Extraction methods, identification and detection of bioactive compounds from plant extracts","volume":"6","author":"Ingle","year":"2017","journal-title":"J. Pharmacogn. Phytochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.acthis.2012.01.006","article-title":"MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets","volume":"114","author":"Stockert","year":"2012","journal-title":"Acta Histochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ymeth.2013.02.011","article-title":"Determination of apoptotic and necrotic cell death in vitro and in vivo","volume":"61","author":"Grootjans","year":"2013","journal-title":"Methods"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Abed, S.N., Bibi, S., Jan, M., Talha, M., Islam, N.U., Zahoor, M., and Al-Joufi, F.A. (2022). Phytochemical Composition, Antibacterial, Antioxidant and Antidiabetic Potentials of Cydonia oblonga Bark. Molecules, 27.","DOI":"10.3390\/molecules27196360"},{"key":"ref_20","unstructured":"(2025, January 14). Jamovi\u2014Open Statistical Software for the Desktop and Cloud. Available online: https:\/\/www.jamovi.org\/."},{"key":"ref_21","unstructured":"(2025, January 14). R: The R Project for Statistical Computing. Available online: https:\/\/www.r-project.org\/."},{"key":"ref_22","unstructured":"Fox, J., Weisberg, S., Price, B., Adler, D., Bates, D., Baud-Bovy, G., Bolker, B., Ellison, S., Firth, D., and Friendly, M. (2024, December 12). car: Companion to Applied Regression 2024. Available online: https:\/\/r-forge.r-universe.dev\/car."},{"key":"ref_23","unstructured":"Wickham, H., Chang, W., Henry, L., Pedersen, T.L., Takahashi, K., Wilke, C., Woo, K., Yutani, H., Dunnington, D., and van den Brand, T. (2024, December 15). ggplot2: Create Elegant Data Visualisations Using the Grammar of Graphics 2024. Available online: https:\/\/ggplot2.tidyverse.org\/reference\/ggplot2-package.html."},{"key":"ref_24","unstructured":"Patil, I., and Powell, C. (2024, December 01). ggstatsplot: \u201cggplot2\u201d Based Plots with Statistical Details 2024. Available online: https:\/\/indrajeetpatil.r-universe.dev\/ggstatsplot."},{"key":"ref_25","first-page":"307","article-title":"Onkoloji Hastalar\u0131nda Tamamlay\u0131c\u0131 ve Alternatif T\u0131p Kullan\u0131m S\u0131kl\u0131\u011f\u0131n\u0131n ve Diyet Yakla\u015f\u0131mlar\u0131n\u0131n Belirlenmesi","volume":"21","author":"Uzsoy","year":"2021","journal-title":"Avrupa Bilim Ve Teknol. Derg."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nahar, J., Boopathi, V., Rupa, E.J., Awais, M., Valappil, A.K., Morshed, M.N., Murugesan, M., Akter, R., Yang, D.U., and Mathiyalagan, R. (2023). Protective Effects of Aquilaria agallocha and Aquilaria malaccensis Edible Plant Extracts against Lung Cancer, Inflammation, and Oxidative Stress\u2014In Silico and In Vitro Study. Appl. Sci., 13.","DOI":"10.3390\/app13106321"},{"key":"ref_27","first-page":"24","article-title":"Analysis of essential oil of eaglewood tree (Aquilaria agallocha Roxb.) by gas chromatography mass spectrometry","volume":"4","author":"Bhuiyan","year":"2009","journal-title":"Bangladesh J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jtcme.2015.12.006","article-title":"Hepatoprotective potential of ethanolic extract of Aquilaria agallocha leaves against paracetamol induced hepatotoxicity in SD rats","volume":"7","author":"Alam","year":"2017","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_29","first-page":"5","article-title":"Antioxidant activity of ethyl acetate extract of Aquilaria agallocha on nitrite-induced methaemoglobin formation P","volume":"2","author":"Miniyar","year":"2008","journal-title":"Int. J. Green Pharm. IJGP"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1111\/1750-3841.16613","article-title":"Evaluation of antioxidant films of chitosan with Aquilaria agallocha extract as packaging material","volume":"88","author":"Karkar","year":"2023","journal-title":"J. Food Sci."},{"key":"ref_31","first-page":"4","article-title":"The screening of phytochemical and antioxidant activity of agarwood leaves (Aquilaria malaccensis) from two sites in North Sumatra, Indonesia","volume":"21","author":"Batubara","year":"2020","journal-title":"Biodiversitas J. Biol. Divers."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11808","DOI":"10.3390\/molecules200711808","article-title":"The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene \u03b2-Caryophyllene from the Essential Oil of Aquilaria crassna","volume":"20","author":"Dahham","year":"2015","journal-title":"Molecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.bcp.2006.02.009","article-title":"Molecular targets of dietary agents for prevention and therapy of cancer","volume":"71","author":"Aggarwal","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/0076-6879(94)34128-1","article-title":"[57] Antioxidant properties of aminosalicylates","volume":"Volume 234","author":"Miles","year":"1994","journal-title":"Methods in Enzymology"},{"key":"ref_35","first-page":"437","article-title":"Evaluation of free radical scavenging and pancreatic lipase inhibitory effects of Aquilaria agallocha extracts","volume":"22","author":"Lee","year":"2015","journal-title":"Food Sci. Preserv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"178","DOI":"10.21010\/ajtcam.v13i5.23","article-title":"In vitro antimicrobial screening of Aquilaria agallocha roots","volume":"13","author":"Yetgin","year":"2016","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_37","first-page":"89","article-title":"(PDF) Ethanolic Stem Extract of Excoecaria agallocha Induces G1 Arrest or Apoptosis in Human Lung Cancer Cells Depending on Their P53 Status","volume":"52","author":"Patil","year":"2012","journal-title":"Taiwania"},{"key":"ref_38","first-page":"9","article-title":"Screening of antioxidant and antifilarial activity of leaf extracts of Excoecaria agallocha L.","volume":"7","author":"Patra","year":"2009","journal-title":"Int. J. Integr. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wang, S., Yu, Z., Wang, C., Wu, C., Guo, P., and Wei, J. (2018). Chemical Constituents and Pharmacological Activity of Agarwood and Aquilaria Plants. Molecules, 23.","DOI":"10.3390\/molecules23020342"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, J., Xiao, S., Cai, Q., Miao, J., and Li, J. (2024, December 03). Antioxidant Capacity and Protective Effects on H2O2-Induced Oxidative Damage in PC12 Cells of the Active Fraction of Brassica rapa L., Available online: http:\/\/ouci.dntb.gov.ua\/en\/works\/9jA6MAVl\/.","DOI":"10.3390\/foods12102075"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0378-8741(97)00075-5","article-title":"Effect of the aqueous extract of Aquilaria agallocha stems on the immediate hypersensitivity reactions","volume":"58","author":"Kim","year":"1997","journal-title":"J. Ethnopharmacol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/651\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:15:17Z","timestamp":1760030117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/651"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":41,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["life15040651"],"URL":"https:\/\/doi.org\/10.3390\/life15040651","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,4,16]]}}}