{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:14:13Z","timestamp":1786115653744,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Fund 2568","award":["207563\/R68EX00173"],"award-info":[{"award-number":["207563\/R68EX00173"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Lymphoma remains a major hematological malignancy associated with treatment resistance and systemic toxicity, highlighting the need for novel anticancer agents derived from natural products. In this study, dicentrine (5), an aporphine alkaloid isolated from Stephania venosa, was investigated for its anti-lymphoma activity in Raji and Ramos cells. Among the isolated compounds, dicentrine (5) exhibited the strongest cytotoxic activity, with IC50 values of 9.03 \u00b1 0.53 and 5.16 \u00b1 0.44 \u00b5g\/mL in Raji and Ramos cells, respectively, while demonstrating favorable selectivity toward lymphoma cells relative to peripheral blood mononuclear cells (PBMCs). Dicentrine (5) significantly suppressed c-Myc and phosphorylated c-Myc expression, reduced lymphoma cell proliferation, and decreased total viable cell numbers in a dose-dependent manner. Cell cycle analysis revealed G0\/G1 arrest in Raji cells and G2\/M arrest in Ramos cells. Furthermore, dicentrine (5) induced apoptosis, as evidenced by increased Annexin V-positive populations and elevated cleaved caspase-3 expression. Molecular docking analysis demonstrated strong binding affinities of dicentrine (5) toward Akt, PI3K, caspase-3, and caspase-9, while network pharmacology identified AKT1 and the PI3K\/Akt signaling pathway as potential targets associated with lymphoma suppression. Western blot analysis further demonstrated that dicentrine (5) significantly reduces total Akt protein expression. Overall, the present findings indicate that dicentrine (5) suppresses lymphoma progression by inhibiting cell proliferation and promoting apoptotic cell death, highlighting its potential as a promising natural therapeutic candidate for lymphoma.<\/jats:p>","DOI":"10.3390\/ijms27156974","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:16:27Z","timestamp":1785766587000},"page":"6974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Pharmacological Characterization of Dicentrine Isolated from Stephania venosa in Human Lymphoma Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0155-9952","authenticated-orcid":false,"given":"Aroonchai","family":"Saiai","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirinya","family":"Moakmamern","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lapamas","family":"Rueankum","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2586-4545","authenticated-orcid":false,"given":"Wenxian","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-3715","authenticated-orcid":false,"given":"Singkome","family":"Tima","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-5017","authenticated-orcid":false,"given":"Siriporn","family":"Okonogi","sequence":"additional","affiliation":[{"name":"Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawitree","family":"Chiampanichayakul","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7259-4694","authenticated-orcid":false,"given":"Songyot","family":"Anuchapreeda","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in Pharmaceutical Nanotechnology, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.mpmed.2025.02.011","article-title":"Non-Hodgkin lymphoma","volume":"53","author":"Paterson","year":"2025","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41375-021-01204-6","article-title":"Molecular biology of Hodgkin lymphoma","volume":"35","author":"Weniger","year":"2021","journal-title":"Leukemia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.4103\/jfmpc.jfmpc_1037_19","article-title":"Non-Hodgkin\u2019s lymphoma: A review","volume":"9","author":"Singh","year":"2020","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/bjh.19218","article-title":"The ATR inhibitor elimusertib exhibits anti-lymphoma activity and synergizes with the PI3K inhibitor copanlisib","volume":"204","author":"Sartori","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1182\/blood.2023019706","article-title":"Sonrotoclax overcomes BCL2 G101V mutation\u2013induced venetoclax resistance in preclinical models of hematologic malignancy","volume":"143","author":"Liu","year":"2024","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.ccell.2024.04.004","article-title":"Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers","volume":"42","author":"Diepstraten","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121591","DOI":"10.1016\/j.indcrop.2025.121591","article-title":"An updated review of isoquinoline alkaloids: Biological activity and mode of action, structural modifications, and agricultural applications","volume":"234","author":"Yang","year":"2025","journal-title":"Ind. Crops Prod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2174\/1568011053174864","article-title":"Cytotoxic and antitumor potentialities of aporphinoid alkaloids","volume":"5","author":"Stevigny","year":"2005","journal-title":"Curr. Med. Chem.-Anti-Cancer Agents"},{"key":"ref_9","first-page":"100257","article-title":"Dicentrine and its N-oxide derivatives induces apoptotic and necrotic cell death in prostate cancer cell lines","volume":"13","author":"Machado","year":"2025","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115248","DOI":"10.1016\/j.jep.2022.115248","article-title":"Alkaloids in genus stephania (Menispermaceae): A comprehensive review of its ethnopharmacology, phytochemistry, pharmacology and toxicology","volume":"293","author":"Wang","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","first-page":"150","article-title":"Anticancer and antioxidative activities of Stephania venosa","volume":"51","author":"Leewanich","year":"2011","journal-title":"Eur. J. Sci. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ooppachai, C., Limtrakul, P., and Yodkeeree, S. (2019). Dicentrine potentiates TNF-\u03b1-induced apoptosis and suppresses invasion of A549 lung adenocarcinoma cells via modulation of NF-\u03baB and AP-1 activation. Molecules, 24.","DOI":"10.3390\/molecules24224100"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/s10600-020-03096-x","article-title":"Bioactive alkaloids of stephania sinica showing anti-drug-resistance activity","volume":"56","author":"Wang","year":"2020","journal-title":"Chem. Nat. Compd."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1007\/s10600-018-2597-3","article-title":"Aporphine alkaloids from Stephania dielsiana","volume":"54","author":"Zhou","year":"2018","journal-title":"Chem. Nat. Compd."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2001022","DOI":"10.1002\/cbdv.202001022","article-title":"Aporphine alkaloids from Ocotea puberula with anti-Trypanosoma cruzi potential\u2013activity of dicentrine-\u03b2-N-Oxide in the plasma membrane electric potentials","volume":"18","author":"Barbosa","year":"2021","journal-title":"Chem. Biodivers."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.3844\/ajassp.2010.1057.1065","article-title":"Antiproliferative effects of alkaloids isolated from the tuber of Stephania venosa via the induction of cell cycle arrest in mammalian cancer cell lines","volume":"7","author":"Nantapap","year":"2010","journal-title":"Am. J. Appl. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0031-9422(03)00240-1","article-title":"Characterisation of alkaloids from some Australian Stephania (Menispermaceae) species","volume":"63","author":"Blanchfield","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/ptr.5861","article-title":"Stephanine from Stephania venosa (Blume) spreng showed effective antiplasmodial and anticancer activities, the latter by inducing apoptosis through the reverse of mitotic exit","volume":"31","author":"Le","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"396","DOI":"10.25135\/rnp.231.21.01.1929","article-title":"Dicentrine and dicentrinone isolated from Stephania tetrandrae Radix suppress HepG2 proliferation through inhibiting PDI activity","volume":"15","author":"Zhao","year":"2021","journal-title":"Rec. Nat. Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0367-326X(00)00193-3","article-title":"Fungitoxic alkaloids from Hokkaido papaveraceae","volume":"71","author":"Ma","year":"2000","journal-title":"Fitoterapia"},{"key":"ref_21","first-page":"1805","article-title":"Acetylcholinesterase inhibitory activity of alkaloids isolated from Stephania venosa","volume":"11","author":"Kongkiatpaiboon","year":"2016","journal-title":"Nat. Prod. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1211\/jpp.58.5.0015","article-title":"Acetylcholinesterase inhibitors from Stephania venosa tuber","volume":"58","author":"Ingkaninan","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","article-title":"MYC on the path to cancer","volume":"149","author":"Dang","year":"2012","journal-title":"Cell"},{"key":"ref_24","unstructured":"Faiq, A. (2024). WHO Classification of Tumours: Haematolymphoid Tumours, International Agency for Research on Cancer."},{"key":"ref_25","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_27","first-page":"4103","article-title":"Medicinal plants: Their use in anticancer treatment","volume":"6","author":"Greenwell","year":"2015","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature11378","article-title":"Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics","volume":"490","author":"Schmitz","year":"2012","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7824","DOI":"10.1073\/pnas.79.24.7824","article-title":"Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells","volume":"79","author":"Bregni","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12420","DOI":"10.1073\/pnas.1305656110","article-title":"PTEN loss defines a PI3K\/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma","volume":"110","author":"Pfeifer","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB signaling: Navigating the network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K pathway in human disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rueankham, L., Panyajai, P., Saiai, A., Rungrojsakul, M., Tima, S., Chiampanichayakul, S., Yeerong, K., Somwongin, S., Chaiyana, W., and Dejkriengkraikul, P. (2023). Biological activities of extracts and compounds from Thai Kae-Lae (Maclura cochinchinensis (Lour.) Corner). BMC Complement. Med. Ther., 23.","DOI":"10.1186\/s12906-023-03979-w"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.fitote.2008.06.007","article-title":"Cytotoxic activity screening of some indigenous Thai plants","volume":"79","author":"Prayong","year":"2008","journal-title":"Fitoterapia"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lica, J.J., Wiecz\u00f3r, M., Grabe, G.J., Heldt, M., Jancz, M., Misiak, M., Gucwa, K., Brankiewicz, W., Maciejewska, N., and Stupak, A. (2021). Effective drug concentration and selectivity depends on fraction of primitive cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094931"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:36:48Z","timestamp":1785991008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":38,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156974"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156974","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}