{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:22Z","timestamp":1785435742025,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"crossref","award":["214479"],"award-info":[{"award-number":["214479"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"crossref"}]},{"award":["214479"],"award-info":[{"award-number":["214479"]}],"id":[{"id":"https:\/\/ror.org\/05m2fqn25","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"crossref","award":["FRB690042\/0162"],"award-info":[{"award-number":["FRB690042\/0162"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FRB690042\/0162"],"award-info":[{"award-number":["FRB690042\/0162"]}],"id":[{"id":"https:\/\/ror.org\/000025p04","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lymphoma is a hematological malignancy and a major non-communicable disease characterized by the uncontrolled proliferation of lymphoid cells, frequently associated with dysregulation of the cellular myelocytomatosis (c-Myc) oncogenic pathway. In this study, we investigated the anti-lymphoma potential of bioactive compounds derived from edible plants in the Zingiberaceae family, including fingerroot (Boesenbergia rotunda), turmeric (Curcuma longa), white turmeric (Curcuma mangga), zedoary (Curcuma zedoaria), and ginger (Zingiber officinale). Crude extracts from these traditionally consumed medicinal food plants were evaluated for cytotoxic effects against human B-cell lymphoma cell lines (Raji and Daudi) and compared with normal peripheral blood mononuclear cells (PBMCs). Among the tested extracts, ginger and turmeric exhibited selective cytotoxicity toward lymphoma cells. Ginger was selected for further investigation, and subsequent analyses identified 6-shogaol as the principal active compound. 6-Shogaol significantly suppressed total and phosphorylated c-Myc protein expression, induced dose-dependent apoptosis, and caused cell cycle arrest in lymphoma cells. Network pharmacology and pathway enrichment analyses suggested the modulation of multiple oncogenic signaling pathways, particularly the PI3K\/Akt\/c-Myc and MAPK signaling. These findings indicate that 6-shogaol exerts anti-lymphoma activity through the coordinated modulation of oncogenic and apoptotic pathways. However, as this study is limited to in vitro and computational analyses, further in vivo validation is required. Overall, 6-shogaol represents a promising food-derived lead compound for the development of novel therapeutic strategies against lymphoma.<\/jats:p>","DOI":"10.3390\/ijms27104168","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T14:05:46Z","timestamp":1778162746000},"page":"4168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["6-Shogaol from Zingiber officinale Induces Cell Cycle Arrest via Suppression of c-Myc Protein Expression and Promotes Apoptosis in Human B-Cell Lymphoma"],"prefix":"10.3390","volume":"27","author":[{"given":"Sirinya","family":"Moakmamern","sequence":"first","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":"Rueankham","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, 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\/0009-0004-7955-3712","authenticated-orcid":false,"given":"Natsima","family":"Viriyaadhammaa","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":"Wenxian","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical 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Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6402-7195","authenticated-orcid":false,"given":"Yupanun","family":"Wutti-In","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, 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\/0000-0002-3452-8511","authenticated-orcid":false,"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":"Cancer Research Unit of Associated Medical Sciences (AMS CRU), 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-3089","authenticated-orcid":false,"given":"Nutjeera","family":"Intasai","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, 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"},{"name":"Center of Excellence in Pharmaceutical Nanotechnology, 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"}]},{"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":"Cancer Research Unit of Associated Medical Sciences (AMS CRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in 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185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1001\/jamaoncol.2016.5688","article-title":"Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study","volume":"3","author":"Global","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_4","unstructured":"(2026, May 05). Cancer in Thailand vol.x, 2016\u20132018. Available online: https:\/\/nci.go.th\/files\/cancer_stat\/1771381927_file.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S0140-6736(16)32407-2","article-title":"Non-Hodgkin lymphoma","volume":"390","author":"Armitage","year":"2017","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/hon.2392","article-title":"Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand","volume":"36","author":"Intragumtornchai","year":"2018","journal-title":"Hematol. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nguyen, L., Papenhausen, P., and Shao, H. (2017). The role of c-MYC in B-cell lymphomas: Diagnostic and molecular Aspects. Genes, 8.","DOI":"10.3390\/genes8040116"},{"key":"ref_8","first-page":"27","article-title":"Developments in Burkitt\u2019s lymphoma: Novel cooperations in oncogenic MYC signaling","volume":"6","author":"Spender","year":"2014","journal-title":"Cancer Manag. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1200\/JCO-25-00690","article-title":"Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma","volume":"43","author":"Wang","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa2408771","article-title":"Enhanced CAR T-cell therapy for lymphoma after previous failure","volume":"392","author":"Svoboda","year":"2025","journal-title":"New Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Garza, N.E., Quintanilla-Licea, R., Romo-S\u00e1enz, C.I., Elizondo-Luevano, J.H., Tamez-Guerra, P., Rodr\u00edguez-Padilla, C., and Gomez-Flores, R. (2023). In vitro biological activity and lymphoma cell growth inhibition by selected Mexican medicinal plants. Life, 13.","DOI":"10.3390\/life13040958"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1038\/s41598-018-21570-z","article-title":"Shikonin exerts antitumor activity in Burkitt\u2019s lymphoma by inhibiting c-MYC and PI3K\/AKT\/mTOR pathway and acts synergistically with doxorubicin","volume":"8","author":"Ni","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1097\/CAD.0b013e3283503fbc","article-title":"Curcumin improves the antitumor effect of X-ray irradiation by blocking the NF-\u03baB pathway: An in-vitro study of lymphoma","volume":"23","author":"Qiao","year":"2012","journal-title":"Anticancer Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s10059-009-0036-9","article-title":"Curcumin induces apoptosis and inhibits growth of human Burkitt\u2019s lymphoma in xenograft mouse model","volume":"20","author":"Li","year":"2009","journal-title":"Mol. Cells"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1080\/01635581.2019.1598565","article-title":"Dietary turmeric bisdemethoxycurcumin suppresses Wilms\u2019 Tumor 1 and CD34 protein expressions in KG-1a leukemic stem cells","volume":"71","author":"Panyajai","year":"2019","journal-title":"Nutr. Cancer."},{"key":"ref_17","first-page":"641","article-title":"Effects of 6-gingerol, an antioxidant from ginger, on inducing apoptosis in human leukemic HL-60 cells","volume":"17","author":"Wang","year":"2003","journal-title":"In Vivo"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.freeradbiomed.2013.12.016","article-title":"(6)-Gingerol-induced myeloid leukemia cell death is initiated by reactive oxygen species and activation of miR-27b expression","volume":"68","author":"Rastogi","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10645","DOI":"10.1021\/jf9027443","article-title":"Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols","volume":"57","author":"Sang","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","first-page":"56","article-title":"Zerumbone induces growth inhibition of Burkitt\u2019s lymphoma cell line via apoptosis","volume":"8","author":"Albaayit","year":"2021","journal-title":"Nat. Volatiles Essent. Oils"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/bs.podrm.2020.07.005","article-title":"Validation of in-vitro bioassay methods: Application in herbal drug research","volume":"46","author":"Indrayanto","year":"2021","journal-title":"Profiles Drug Subst. Excip. Relat. Methodol."},{"key":"ref_22","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 eelectivity depends on fraction of primitive cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094931"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Panyajai, P., Viriyaadhammaa, N., Chiampanichayakul, S., Sakamoto, Y., Okonogi, S., Moroishi, T., and Anuchapreeda, S. (2025). Anticancer and cancer preventive activities of shogaol and curcumin from Zingiberaceae family plants in KG-1a leukemic stem cells. BMC Complement. Med. Ther., 25.","DOI":"10.1186\/s12906-025-04829-7"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mao, Q.Q., Xu, X.Y., Cao, S.Y., Gan, R.Y., Corke, H., Beta, T., and Li, H.B. (2019). Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods, 8.","DOI":"10.3390\/foods8060185"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bischoff-Kont, I., and F\u00fcrst, R. (2021). Benefits of ginger and its constituent 6-Shogaol in inhibiting inflammatory processes. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060571"},{"key":"ref_26","first-page":"790","article-title":"Effect of salicylic acid application on biochemical changes in ginger (Zingiber officinale Roscoe)","volume":"6","author":"Ghasemzadeh","year":"2012","journal-title":"J. Med. Plants Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1158\/1055-9965.EPI-07-2934","article-title":"Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects","volume":"17","author":"Zick","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.fct.2017.02.038","article-title":"Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cells","volume":"109","author":"Zhang","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Liu, C.M., Kao, C.L., Tseng, Y.T., Lo, Y.C., and Chen, C.Y. (2017). Ginger phytochemicals inhibit cell growth and modulate drug resistance factors in Docetaxel resistant prostate cancer cell. Molecules, 22.","DOI":"10.3390\/molecules22091477"},{"key":"ref_30","first-page":"701","article-title":"Attenuation of autophagy flux by 6-shogaol sensitizes human liver cancer cells to TRAIL-induced apoptosis via p53 and ROS","volume":"43","author":"Nazim","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_31","first-page":"2161","article-title":"p53 mutations in Raji cells: Characterization and localization relative to other Burkitt\u2019s lymphomas","volume":"7","author":"Duthu","year":"1992","journal-title":"Oncogene"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1039\/c2fo30252g","article-title":"Antiproliferative activities of tea and herbal infusions","volume":"4","author":"Li","year":"2013","journal-title":"Food Funct."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4168\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:43:04Z","timestamp":1778301784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104168"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104168","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]}}}