{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:02:40Z","timestamp":1779926560406,"version":"3.53.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":52,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003459","name":"Guizhou University","doi-asserted-by":"crossref","award":["No. [2020]075"],"award-info":[{"award-number":["No. [2020]075"]}],"id":[{"id":"10.13039\/501100003459","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Science and Technology Department of Guizhou Province","award":["No. ZK[2022]-general-161"],"award-info":[{"award-number":["No. ZK[2022]-general-161"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-47527-1","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T15:53:51Z","timestamp":1775490831000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel L-shaped ortho-quinone analog and 2-Deoxy-D-Glucose a synergistic approach to inhibit hepatocellular carcinoma cell proliferation"],"prefix":"10.1038","volume":"16","author":[{"given":"Xiang","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmei","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"issue":"1","key":"47527_CR1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s43556-024-00239-2","volume":"6","author":"Y Gu","year":"2025","unstructured":"Gu, Y. et al. Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer. Mol. Biomed. 6 (1), 2. https:\/\/doi.org\/10.1186\/s43556-024-00239-2 (2025).","journal-title":"Mol. Biomed."},{"issue":"6","key":"47527_CR2","doi-asserted-by":"publisher","first-page":"e09519","DOI":"10.1016\/j.heliyon.2022.e09519","volume":"8","author":"AM Casta\u00f1eda","year":"2022","unstructured":"Casta\u00f1eda, A. M., Mel\u00e9ndez, C. M., Uribe, D. & Pedroza-D\u00edaz, J. Synergistic effects of natural compounds and conventional chemotherapeutic agents: recent insights for the development of cancer treatment strategies. Heliyon 8 (6), e09519. https:\/\/doi.org\/10.1016\/j.heliyon.2022.e09519 (2022).","journal-title":"Heliyon"},{"key":"47527_CR3","doi-asserted-by":"publisher","unstructured":"Singh, R., Gupta, V., Kumar, A. & Singh, K. 2-Deoxy-D-Glucose: a novel pharmacological agent for killing hypoxic tumor cells, oxygen dependence-lowering in Covid-19, and other pharmacological activities. Adv. Pharmacol. Pharm. Sci. 2023, 20239993386. https:\/\/doi.org\/10.1155\/2023\/9993386 (2023).","DOI":"10.1155\/2023\/9993386"},{"issue":"5","key":"47527_CR4","doi-asserted-by":"publisher","first-page":"3706","DOI":"10.1021\/acs.jmedchem.1c01737","volume":"65","author":"YS Wijayasinghe","year":"2022","unstructured":"Wijayasinghe, Y. S. et al. A comprehensive biological and synthetic perspective on 2-Deoxy-d-Glucose (2-DG), a sweet molecule with therapeutic and diagnostic potentials. J. Med. Chem. 65 (5), 3706\u20133728. https:\/\/doi.org\/10.1021\/acs.jmedchem.1c01737 (2022).","journal-title":"J. Med. Chem."},{"key":"47527_CR5","doi-asserted-by":"publisher","first-page":"5359","DOI":"10.2147\/ott.S212465","volume":"12","author":"L Wang","year":"2019","unstructured":"Wang, L., Yang, Q., Peng, S. & Liu, X. The combination of the glycolysis inhibitor 2-DG and sorafenib can be effective against sorafenib-tolerant persister cancer cells. Onco Targets Ther. 12, 5359\u20135373. https:\/\/doi.org\/10.2147\/ott.S212465 (2019).","journal-title":"Onco Targets Ther."},{"issue":"1","key":"47527_CR6","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12935-022-02624-9","volume":"22","author":"P Dhyani","year":"2022","unstructured":"Dhyani, P. et al. Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer Cell. Int. 22 (1), 206. https:\/\/doi.org\/10.1186\/s12935-022-02624-9 (2022).","journal-title":"Cancer Cell. Int."},{"issue":"6","key":"47527_CR7","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s12032-025-02767-5","volume":"42","author":"R Wang","year":"2025","unstructured":"Wang, R. et al. A novel L-shaped ortho-quinone analog targeting adenosine A2b receptor to inhibit epithelial-mesenchymal transition in colorectal cancer cells. Med. Oncol. 42 (6), 197. https:\/\/doi.org\/10.1007\/s12032-025-02767-5 (2025).","journal-title":"Med. Oncol."},{"issue":"1","key":"47527_CR8","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s13020-025-01124-y","volume":"20","author":"D Cui","year":"2025","unstructured":"Cui, D. et al. Natural anti-cancer products: insights from herbal medicine. Chin. Med. 20 (1), 82. https:\/\/doi.org\/10.1186\/s13020-025-01124-y (2025).","journal-title":"Chin. Med."},{"issue":"6","key":"47527_CR9","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1001\/jamaoncol.2024.0591","volume":"10","author":"M Hussain","year":"2024","unstructured":"Hussain, M. et al. Metastatic hormone-sensitive prostate cancer and combination treatment outcomes: a review. JAMA Oncol. 10 (6), 807\u2013820. https:\/\/doi.org\/10.1001\/jamaoncol.2024.0591 (2024).","journal-title":"JAMA Oncol."},{"key":"47527_CR10","doi-asserted-by":"publisher","unstructured":"Man, S. et al. Treatment for liver cancer: from sorafenib to natural products. Eur. J. Med. Chem. 224, 113690. https:\/\/doi.org\/10.1016\/j.ejmech.2021.113690 (2021).","DOI":"10.1016\/j.ejmech.2021.113690"},{"key":"47527_CR11","doi-asserted-by":"publisher","unstructured":"Saghatelyan, T. et al. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: a comparative, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 70, 153218. https:\/\/doi.org\/10.1016\/j.phymed.2020.153218 (2020).","DOI":"10.1016\/j.phymed.2020.153218"},{"key":"47527_CR12","doi-asserted-by":"publisher","unstructured":"Wu, J., Li, Y., He, Q. & Yang, X. Exploration of the use of natural compounds in combination with chemotherapy drugs for tumor treatment. Molecules 28, 3. https:\/\/doi.org\/10.3390\/molecules28031022 (2023).","DOI":"10.3390\/molecules28031022"},{"key":"47527_CR13","doi-asserted-by":"publisher","unstructured":"Xie, F. et al. Efficacy and safety of Salvia miltiorrhiza (Salvia miltiorrhiza Bunge) and ligustrazine injection in the adjuvant treatment of early-stage diabetic kidney disease: a systematic review and meta-analysis. J. Ethnopharmacol. 2021, 281114346. https:\/\/doi.org\/10.1016\/j.jep.2021.114346 (2021).","DOI":"10.1016\/j.jep.2021.114346"},{"key":"47527_CR14","doi-asserted-by":"publisher","first-page":"4735","DOI":"10.2147\/dddt.S266911","volume":"14","author":"R Guo","year":"2020","unstructured":"Guo, R. et al. Pharmacological activity and mechanism of tanshinone IIA in related diseases. Drug Des. Dev. Ther. 14, 4735\u20134748. https:\/\/doi.org\/10.2147\/dddt.S266911 (2020).","journal-title":"Drug Des. Dev. Ther."},{"key":"47527_CR15","doi-asserted-by":"publisher","unstructured":"Jiang, Z., Gao, W. & Huang, L. Tanshinones critical pharmacological components in salvia miltiorrhiza. Front. Pharmacol. 10, 202. https:\/\/doi.org\/10.3389\/fphar.2019.00202 (2019).","DOI":"10.3389\/fphar.2019.00202"},{"key":"47527_CR16","doi-asserted-by":"publisher","unstructured":"Munagala, R., Aqil, F., Jeyabalan, J., Gupta, R. C. & Part, B. Tanshinone IIA inhibits viral oncogene expression leading to apoptosis and inhibition of cervical cancer. Cancer Lett. 356, 536\u2013546. https:\/\/doi.org\/10.1016\/j.canlet.2014.09.037 (2015).","DOI":"10.1016\/j.canlet.2014.09.037"},{"key":"47527_CR17","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-03857-x","author":"H Shahrokhi","year":"2025","unstructured":"Shahrokhi, H., Asili, J., Tayarani-Najaran, Z. & Boozari, M. Signaling pathways behind the biological effects of tanshinone IIA for the prevention of cancer and cardiovascular diseases. Naunyn Schmiedebergs Arch. Pharmacol. https:\/\/doi.org\/10.1007\/s00210-025-03857-x (2025).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"issue":"6","key":"47527_CR18","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s12272-011-0612-3","volume":"34","author":"X Zhao","year":"2011","unstructured":"Zhao, X., Liu, X., Gan, L., Zhou, C. & Mo, J. Preparation and physicochemical characterizations of tanshinone IIA solid dispersion. Arch. Pharm. Res. 34 (6), 949\u2013959. https:\/\/doi.org\/10.1007\/s12272-011-0612-3 (2011).","journal-title":"Arch. Pharm. Res."},{"key":"47527_CR19","doi-asserted-by":"publisher","unstructured":"Li, S. Y. et al. Potent cytotoxicity of novel L-shaped ortho-quinone analogs through inducing apoptosis. Molecules 24, 22. https:\/\/doi.org\/10.3390\/molecules24224138 (2019).","DOI":"10.3390\/molecules24224138"},{"key":"47527_CR20","doi-asserted-by":"publisher","unstructured":"Yu, J. et al. Design, synthesis, and evaluation of proliferation inhibitory activity of novel L-shaped ortho-quinone analogs as anticancer agents. Bioorg. Chem. 117, 105383. https:\/\/doi.org\/10.1016\/j.bioorg.2021.105383 (2021).","DOI":"10.1016\/j.bioorg.2021.105383"},{"issue":"1","key":"47527_CR21","doi-asserted-by":"publisher","first-page":"5518","DOI":"10.1038\/srep05518","volume":"4","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. Eupolyphaga sinensis Walker displays inhibition on hepatocellular carcinoma through regulating cell growth and metastasis signaling. Sci. Rep. 4 (1), 5518. https:\/\/doi.org\/10.1038\/srep05518 (2014).","journal-title":"Sci. Rep."},{"key":"47527_CR22","doi-asserted-by":"publisher","unstructured":"Xu, L. et al. Chenodeoxycholic acid (CDCA) promoted intestinal epithelial cell proliferation by regulating cell cycle progression and mitochondrial biogenesis in IPEC-J2 Cells. Antioxid. (Basel). 11, 11. https:\/\/doi.org\/10.3390\/antiox11112285 (2022).","DOI":"10.3390\/antiox11112285"},{"issue":"3","key":"47527_CR23","doi-asserted-by":"publisher","first-page":"e00149","DOI":"10.1002\/prp2.149","volume":"3","author":"J Foucquier","year":"2015","unstructured":"Foucquier, J. & Guedj, M. Analysis of drug combinations: current methodological landscape. Pharmacol. Res. Perspect. 3 (3), e00149. https:\/\/doi.org\/10.1002\/prp2.149 (2015).","journal-title":"Pharmacol. Res. Perspect."},{"issue":"18","key":"47527_CR24","doi-asserted-by":"publisher","first-page":"e123","DOI":"10.1093\/nar\/gkp596","volume":"37","author":"D Parkhomchuk","year":"2009","unstructured":"Parkhomchuk, D. et al. Transcriptome analysis by strand-specific sequencing of complementary DNA. Nucleic Acids Res. 37 (18), e123. https:\/\/doi.org\/10.1093\/nar\/gkp596 (2009).","journal-title":"Nucleic Acids Res."},{"key":"47527_CR25","doi-asserted-by":"publisher","unstructured":"Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol. 11 (10), R106. https:\/\/doi.org\/10.1186\/gb-2010-11-10-r106 (2010).","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"47527_CR26","doi-asserted-by":"publisher","unstructured":"Coates, D. E. et al. Quantitative real-time gene profiling of human alveolar osteoblasts using a one-step system. In Oral Biology: Molecular Techniques and Applications (eds. Seymour, G. J. & Cullinn, M. P.) 417\u2009\u2013\u2009447 (Springer, 2023). https:\/\/doi.org\/10.1007\/978-1-0716-2780-8_24.","DOI":"10.1007\/978-1-0716-2780-8_24"},{"issue":"3","key":"47527_CR27","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.cell.2015.10.001","volume":"163","author":"GS Shadel","year":"2015","unstructured":"Shadel, G. S. & Horvath, T. L. Mitochondrial ROS signaling in organismal homeostasis. Cell 163 (3), 560\u2013569. https:\/\/doi.org\/10.1016\/j.cell.2015.10.001 (2015).","journal-title":"Cell"},{"issue":"2","key":"47527_CR28","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","volume":"20","author":"G Hoxhaj","year":"2020","unstructured":"Hoxhaj, G. & Manning, B. D. The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat. Rev. Cancer. 20 (2), 74\u201388. https:\/\/doi.org\/10.1038\/s41568-019-0216-7 (2020).","journal-title":"Nat. Rev. Cancer"},{"issue":"21","key":"47527_CR29","doi-asserted-by":"publisher","first-page":"907","DOI":"10.4254\/wjh.v9.i21.907","volume":"9","author":"M Le Grazie","year":"2017","unstructured":"Le Grazie, M., Biagini, M. R., Tarocchi, M., Polvani, S. & Galli, A. Chemotherapy for hepatocellular carcinoma: the present and the future. World J. Hepatol. 9 (21), 907\u2013920. https:\/\/doi.org\/10.4254\/wjh.v9.i21.907 (2017).","journal-title":"World J. Hepatol."},{"key":"47527_CR30","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.2147\/jhcS54458","volume":"12","author":"QB Wang","year":"2025","unstructured":"Wang, Q. B. et al. Tumor compression of the hepatic or portal vein predicts the presence of microvascular invasion and satellite nodules in hepatocellular carcinoma: a retrospective study. J. Hepatocell Carcinoma. 12, 2055\u20132067. https:\/\/doi.org\/10.2147\/jhcS54458 (2025).","journal-title":"J. Hepatocell Carcinoma"},{"key":"47527_CR31","doi-asserted-by":"publisher","first-page":"2681","DOI":"10.2147\/jhc.S556306","volume":"12","author":"WL Luo","year":"2025","unstructured":"Luo, W. L. et al. Impact of middle hepatic vein resection during hemihepatectomy on surgical outcomes and long-term prognosis in hepatocellular carcinoma: a retrospective study. J. Hepatocell Carcinoma. 12, 2681\u20132692. https:\/\/doi.org\/10.2147\/jhc.S556306 (2025).","journal-title":"J. Hepatocell Carcinoma"},{"key":"47527_CR32","doi-asserted-by":"publisher","unstructured":"Shuvalov, O., Daks, A., Fedorova, O., Petukhov, A. & Barlev, N. Linking metabolic reprogramming, plasticity and tumor progression. Cancers (Basel). 13, 4. https:\/\/doi.org\/10.3390\/cancers13040762 (2021).","DOI":"10.3390\/cancers13040762"},{"key":"47527_CR33","doi-asserted-by":"publisher","unstructured":"Pajak, B. et al. 2-Deoxy-d-Glucose and its analogs: from diagnostic to therapeutic agents. Int. J. Mol. Sci. 21, 1. https:\/\/doi.org\/10.3390\/ijms21010234 (2019).","DOI":"10.3390\/ijms21010234"},{"issue":"3","key":"47527_CR34","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1172\/jci97712","volume":"129","author":"W Wang","year":"2019","unstructured":"Wang, W. et al. MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT\/mTOR signaling. J. Clin. Invest. 129 (3), 1015\u20131029. https:\/\/doi.org\/10.1172\/jci97712 (2019).","journal-title":"J. Clin. Invest."},{"key":"47527_CR35","doi-asserted-by":"publisher","unstructured":"W\u00f3jcik, M. et al. The impact of proinflammatory M1 macrophages on the proliferation and expression of cyclin E2, mitogen-activated protein kinases 4 and 7 in hepatocytes isolated from a diethylnitrosamine-induced hepatocellular carcinoma rat model. Molecules 30, 17. https:\/\/doi.org\/10.3390\/molecules30173657 (2025).","DOI":"10.3390\/molecules30173657"},{"issue":"9","key":"47527_CR36","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1111\/febs.17283","volume":"292","author":"K Dahm","year":"2025","unstructured":"Dahm, K., Vijayarangakannan, P., Wollscheid, H. P., Schild, H. & Rajalingam, K. Atypical MAPKs in cancer. Febs J. 292 (9), 2173\u20132188. https:\/\/doi.org\/10.1111\/febs.17283 (2025).","journal-title":"Febs J."},{"issue":"1","key":"47527_CR37","doi-asserted-by":"publisher","first-page":"157","DOI":"10.14336\/ad.2021.0729","volume":"13","author":"X Xie","year":"2022","unstructured":"Xie, X. et al. The emerging roles on mitochondrial function in diseases. Aging Dis. 13 (1), 157\u2013174. https:\/\/doi.org\/10.14336\/ad.2021.0729 (2022).","journal-title":"Aging Dis."},{"issue":"8","key":"47527_CR38","doi-asserted-by":"publisher","first-page":"e3002227","DOI":"10.1371\/journal.pbio.3002227","volume":"21","author":"D Han","year":"2023","unstructured":"Han, D. et al. Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy. PLoS Biol. 21 (8), e3002227. https:\/\/doi.org\/10.1371\/journal.pbio.3002227 (2023).","journal-title":"PLoS Biol."},{"key":"47527_CR39","doi-asserted-by":"publisher","unstructured":"Chen, X. M. et al. ZG16B: a key regulator of tumor progression and immune microenvironment modulation in cancer (Review). Int. J. Mol. Med. 57, 3. https:\/\/doi.org\/10.3892\/ijmm.2026.5729 (2026).","DOI":"10.3892\/ijmm.2026.5729"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-47527-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-47527-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-47527-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:07:25Z","timestamp":1779923245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-47527-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["47527"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-47527-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"24 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All animal experiments were conducted according to the guidelines and requirements of the Ethics Committee of Guizhou University (No: EAE-GZU-2023-E039).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"16498"}}