{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T20:12:44Z","timestamp":1770063164881,"version":"3.49.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.<\/jats:p>","DOI":"10.1038\/srep44685","type":"journal-article","created":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T11:21:30Z","timestamp":1490095290000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Vidatox 30 CH has tumor activating effect in hepatocellular carcinoma"],"prefix":"10.1038","volume":"7","author":[{"given":"Catia","family":"Giovannini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Baglioni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Baron Toaldo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Cescon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Bolondi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Gramantieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,3,21]]},"reference":[{"key":"BFsrep44685_CR1","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1200\/JCO.2005.11.922","volume":"23","author":"BR Cassileth","year":"2005","unstructured":"Cassileth, B. R. & Vickers, A. J. High prevalence of complementary and alternative medicine use among cancer patients: implications for research and clinical care. J. Clin. Oncol. 23, 2590\u20132592 (2005).","journal-title":"J. Clin. Oncol."},{"key":"BFsrep44685_CR2","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1007\/s00432-014-1656-9","volume":"140","author":"AC Conrad","year":"2014","unstructured":"Conrad, A. C. et al. Attitudes of members of the German Society for Palliative Medicine toward complementary and alternative medicine for cancer patients. J. Cancer Res. Clin. Oncol. 140, 1229\u20131237 (2014).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"BFsrep44685_CR3","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1177\/1534735403256207","volume":"2","author":"J Eng","year":"2003","unstructured":"Eng, J. et al. A population-based survey of complementary and alternative medicine use in men recently diagnosed with prostate cancer. Integr. Cancer Ther. 2, 212\u2013216 (2003).","journal-title":"Integr. Cancer Ther"},{"key":"BFsrep44685_CR4","first-page":"459","volume":"12","author":"LG Balneaves","year":"2006","unstructured":"Balneaves, L. G., Bottorff, J. L., Hislop, T. G. & Herbert, C. Levels of commitment: exploring complementary therapy use by women with breast cancer. J. Altern. Complement. Med. 12, 459\u2013466 (2006).","journal-title":"Med"},{"key":"BFsrep44685_CR5","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1007\/s11764-016-0530-y","volume":"10","author":"GM John","year":"2016","unstructured":"John, G. M. et al. Complementary and alternative medicine use among US cancer survivors. J. Cancer Surviv. 10, 850\u201364 (2016).","journal-title":"J. Cancer Surviv"},{"key":"BFsrep44685_CR6","doi-asserted-by":"crossref","first-page":"1720239","DOI":"10.1155\/2016\/1720239","volume":"2016","author":"C Hu","year":"2016","unstructured":"Hu, C. et al. Acupuncture for Pain Management in Cancer: A Systematic Review and Meta-Analysis. Evid. Based Complement. Alternat. Med . 2016, 1720239 (2016).","journal-title":"Evid. Based Complement. Alternat. Med"},{"key":"BFsrep44685_CR7","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1002\/1097-0142(20010401)91:7<1390::AID-CNCR1143>3.0.CO;2-C","volume":"91","author":"BR Cassileth","year":"2001","unstructured":"Cassileth, B. R., Schraub, S., Robinson, E. & Vickers, A. Alternative medicine use worldwide: the International Union Against Cancer survey. Cancer 91, 1390\u20131393 (2001).","journal-title":"Cancer"},{"key":"BFsrep44685_CR8","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1111\/j.1365-2702.2011.03732.x","volume":"21","author":"I Aydin Avci","year":"2012","unstructured":"Aydin Avci, I., Koc, Z. & Saglam, Z. Use of complementary and alternative medicine by patients with cancer in northern Turkey: analysis of cost and satisfaction. J. Clin. Nurs. 21, 677\u2013688 (2012).","journal-title":"J. Clin. Nurs"},{"key":"BFsrep44685_CR9","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1634\/theoncologist.9-1-80","volume":"9","author":"BR Cassileth","year":"2004","unstructured":"Cassileth, B. R. & Deng, G. Complementary and alternative therapies for cancer. Oncologist 9, 80\u201389 (2004).","journal-title":"Oncologist"},{"key":"BFsrep44685_CR10","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.ijgo.2015.11.008","volume":"133","author":"I Barco","year":"2016","unstructured":"Barco, I. et al. Advanced breast cancer following alternative medicine. Int. J. Gynaecol. Obstet. 133, 378\u20139 (2016).","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"BFsrep44685_CR11","first-page":"93","volume":"48","author":"A Gomes","year":"2010","unstructured":"Gomes, A. et al. Anticancer potential of animal venoms and toxins. Indian. J. Exp. Biol. 48, 93\u2013103 (2010).","journal-title":"Indian. J. Exp. Biol."},{"key":"BFsrep44685_CR12","first-page":"5","volume":"4","author":"A Diaz-Garcia","year":"2013","unstructured":"Diaz-Garcia, A. et al. In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines. J. Venom Res. 4, 5\u201312 (2013).","journal-title":"J. Venom Res"},{"key":"BFsrep44685_CR13","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1097\/01.cad.0000217422.52208.fa","volume":"17","author":"S Haupt","year":"2006","unstructured":"Haupt, S. & Haupt, Y. Importance of p53 for cancer onset and therapy. Anticancer Drugs 17, 725\u2013732 (2006).","journal-title":"Anticancer Drugs"},{"key":"BFsrep44685_CR14","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2165\/00003495-200969020-00006","volume":"69","author":"GM Keating","year":"2009","unstructured":"Keating, G. M. & Santoro, A. Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs 69, 223\u2013240 (2009).","journal-title":"Drugs"},{"key":"BFsrep44685_CR15","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nrc1627","volume":"5","author":"D Neri","year":"2005","unstructured":"Neri, D. & Bicknell, R. Tumour vascular targeting. Nat. Rev. Cancer 5, 436\u2013446 (2005).","journal-title":"Nat. Rev. Cancer"},{"key":"BFsrep44685_CR16","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1136\/jcp.2010.085142","volume":"64","author":"J Huang","year":"2011","unstructured":"Huang, J. et al. Prognostic significance and potential therapeutic target of VEGFR2 in hepatocellular carcinoma. J. Clin. Pathol. 64, 343\u2013348 (2011).","journal-title":"J. Clin. Pathol."},{"key":"BFsrep44685_CR17","first-page":"1311","volume":"33","author":"WF Mao","year":"2012","unstructured":"Mao, W. F. et al. The important roles of RET, VEGFR2 and the RAF\/MEK\/ERK pathway in cancer treatment with sorafenib. Acta Pharmacol. Sin. 33, 1311\u20131318 (2012).","journal-title":"VEGFR2 and the RAF\/MEK\/ERK pathway in cancer treatment with sorafenib. Acta Pharmacol. Sin"},{"key":"BFsrep44685_CR18","doi-asserted-by":"publisher","first-page":"187204","DOI":"10.1155\/2013\/187204","volume":"2013","author":"D Capece","year":"2013","unstructured":"Capece, D. et al. The inflammatory microenvironment in hepatocellular carcinoma: a pivotal role for tumor-associated macrophages. Biomed. Res. Int. 2013, 187204 (2013).","journal-title":"Biomed. Res. Int."},{"key":"BFsrep44685_CR19","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/nri1703","volume":"5","author":"M Karin","year":"2005","unstructured":"Karin, M. & Greten, F. R. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5, 749\u2013759 (2005).","journal-title":"Nat. Rev. Immunol"},{"key":"BFsrep44685_CR20","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.gde.2009.11.004","volume":"20","author":"SI Grivennikov","year":"2010","unstructured":"Grivennikov, S. I. & Karin, M. Inflammation and oncogenesis: a vicious connection. Curr. Opin. Genet. Dev. 20, 65\u201371 (2010).","journal-title":"Curr. Opin. Genet. Dev"},{"key":"BFsrep44685_CR21","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/j.1432-1033.1995.0349k.x","volume":"229","author":"B Saad","year":"1995","unstructured":"Saad, B., Frei, K., Scholl, F. A., Fontana, A. & Maier, P. Hepatocyte-derived interleukin-6 and tumor-necrosis factor alpha mediate the lipopolysaccharide-induced acute-phase response and nitric oxide release by cultured rat hepatocytes. Eur. J. Biochem. 229, 349\u2013355 (1995).","journal-title":"Eur. J. Biochem"},{"key":"BFsrep44685_CR22","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1002\/(SICI)1097-0142(19980815)83:4<777::AID-CNCR22>3.0.CO;2-O","volume":"83","author":"E Ernst","year":"1998","unstructured":"Ernst, E. & Cassileth, B. R. The prevalence of complementary\/alternative medicine in cancer: a systematic review. Cancer 83, 777\u2013782 (1998).","journal-title":"Cancer"},{"key":"BFsrep44685_CR23","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.1200\/JCO.2000.18.13.2505","volume":"18","author":"MA Richardson","year":"2000","unstructured":"Richardson, M. A., Sanders, T., Palmer, J. L., Greisinger, A. & Singletary, S. E. Complementary\/alternative medicine use in a comprehensive cancer center and the implications for oncology. J. Clin. Oncol. 18, 2505\u20132514 (2000).","journal-title":"J. Clin. Oncol."},{"key":"BFsrep44685_CR24","doi-asserted-by":"publisher","first-page":"31878","DOI":"10.1155\/2013\/318781","volume":"2013","author":"AE Kristoffersen","year":"2013","unstructured":"Kristoffersen, A. E., Norheim, A. J. & Fonnebo, V. M. Complementary and Alternative Medicine Use among Norwegian Cancer Survivors: Gender-Specific Prevalence and Associations for Use. Evid. Based Complement. Alternat. Med. 2013, 31878 (2013).","journal-title":"Evid. Based Complement. Alternat. Med"},{"key":"BFsrep44685_CR25","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1007\/s00520-007-0290-3","volume":"15","author":"L Weeks","year":"2007","unstructured":"Weeks, L., Verhoef, M. & Scott, C. Presenting the alternative: cancer and complementary and alternative medicine in the Canadian print media. Support. Care Cancer 15, 931\u2013938 (2007).","journal-title":"Support. Care Cancer"},{"key":"BFsrep44685_CR26","doi-asserted-by":"publisher","first-page":"2868","DOI":"10.1001\/jama.292.23.2868","volume":"292","author":"RB Saper","year":"2004","unstructured":"Saper, R. B. et al. Heavy metal content of ayurvedic herbal medicine products. JAMA 292, 2868\u20132873 (2004).","journal-title":"JAMA"},{"key":"BFsrep44685_CR27","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1177\/1535370213513991","volume":"239","author":"J Ding","year":"2014","unstructured":"Ding, J., Chua, P. J., Bay, B. H. & Gopalakrishnakone, P. Scorpion venoms as a potential source of novel cancer therapeutic compounds. Exp. Biol. Med. (Maywood) 239, 387\u2013393 (2014).","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"BFsrep44685_CR28","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.toxicon.2011.04.011","volume":"58","author":"BI Garcia-Gomez","year":"2011","unstructured":"Garcia-Gomez, B. I., Coronas, F. I., Restano-Cassulini, R., Rodriguez, R. R. & Possani, L. D. Biochemical and molecular characterization of the venom from the Cuban scorpion Rhopalurus junceus. Toxicon 58, 18\u201327 (2011).","journal-title":"Toxicon"},{"key":"BFsrep44685_CR29","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S0344-0338(96)80088-4","volume":"192","author":"PH Shaw","year":"1996","unstructured":"Shaw, P. H. The role of p53 in cell cycle regulation. Pathol. Res. Pract. 192, 669\u2013675 (1996).","journal-title":"Pathol. Res. Pract"},{"key":"BFsrep44685_CR30","first-page":"3","volume":"36","author":"K Harada","year":"2000","unstructured":"Harada K. & Ogden G. R. An overview of the cell cycle arrest protein, p21(WAF1). Oral. Oncol. 36, 3\u20137 (2000).","journal-title":"An overview of the cell cycle arrest protein, p21(WAF1). Oral. Oncol"},{"key":"BFsrep44685_CR31","doi-asserted-by":"publisher","first-page":"22128","DOI":"10.1074\/jbc.273.34.22128","volume":"273","author":"E Giraudo","year":"1998","unstructured":"Giraudo, E. et al. Tumor necrosis factor-alpha regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells. J. Biol. Chem. 273, 22128\u201322135 (1998).","journal-title":"J. Biol. Chem."},{"key":"BFsrep44685_CR32","doi-asserted-by":"publisher","first-page":"8413","DOI":"10.1074\/jbc.273.14.8413","volume":"273","author":"A Ristimaki","year":"1998","unstructured":"Ristimaki, A., Narko, K., Enholm, B., Joukov, V. & Alitalo, K. Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-C. J. Biol. Chem. 273, 8413\u20138418 (1998).","journal-title":"J. Biol. Chem"},{"key":"BFsrep44685_CR33","first-page":"593","volume":"66","author":"YY Wang","year":"2003","unstructured":"Wang, Y. Y. et al. Increased serum concentrations of tumor necrosis factor-alpha are associated with disease progression and malnutrition in hepatocellular carcinoma. J. Chin. Med. Assoc. 66, 593\u2013598 (2003).","journal-title":"J. Chin. Med. Assoc."},{"key":"BFsrep44685_CR34","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1056\/NEJMoa0708857","volume":"359","author":"JM Llovet","year":"2008","unstructured":"Llovet, J. M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378\u2013390 (2008).","journal-title":"N. Engl. J. Med"},{"key":"BFsrep44685_CR35","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1007\/s00432-013-1460-y","volume":"139","author":"M Paul","year":"2013","unstructured":"Paul, M. et al. Patients with advanced cancer and their usage of complementary and alternative medicine. J. Cancer Res. Clin. Oncol. 139, 1515\u20131522 (2013).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"BFsrep44685_CR36","doi-asserted-by":"publisher","first-page":"11667","DOI":"10.1074\/jbc.M113.540419","volume":"289","author":"Y Song","year":"2014","unstructured":"Song, Y. et al. Sj7170, a unique dual-function peptide with a specific alpha-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom. J. Biol. Chem. 289, 11667\u201311680 (2014).","journal-title":"J. Biol. Chem."},{"key":"BFsrep44685_CR37","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1016\/j.jhep.2008.12.032","volume":"50","author":"C Giovannini","year":"2009","unstructured":"Giovannini, C. et al. Selective ablation of Notch3 in HCC enhances doxorubicin\u2019s death promoting effect by a p53 dependent mechanism. J. Hepatol. 50, 969\u2013979 (2009).","journal-title":"J. Hepatol"},{"key":"BFsrep44685_CR38","doi-asserted-by":"publisher","first-page":"39609","DOI":"10.18632\/oncotarget.9203","volume":"7","author":"C Giovannini","year":"2016","unstructured":"Giovannini, C. et al. Molecular and proteomic insight into Notch1 characterization in hepatocellular carcinoma. Oncotarget 7, 39609\u201330626 (2016).","journal-title":"Oncotarget"},{"key":"BFsrep44685_CR39","doi-asserted-by":"publisher","first-page":"10607","DOI":"10.18632\/oncotarget.2523","volume":"5","author":"C Giovannini","year":"2014","unstructured":"Giovannini, C. et al. Suppression of p53 by Notch3 is mediated by Cyclin G1 and sustained by MDM2 and miR-221 axis in hepatocellular carcinoma. Oncotarget 5, 10607\u201310620 (2014).","journal-title":"Oncotarget"}],"updated-by":[{"DOI":"10.1038\/srep46920","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep44685.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep44685","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep44685.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T14:51:35Z","timestamp":1750171895000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep44685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,21]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,4,28]]}},"alternative-id":["BFsrep44685"],"URL":"https:\/\/doi.org\/10.1038\/srep44685","relation":{"erratum":[{"id-type":"doi","id":"10.1038\/srep46920","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,21]]},"assertion":[{"value":"15 June 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2017","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2017","order":7,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Erratum","order":8,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"An Erratum to this paper has been published:","order":9,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/srep46920","URL":"https:\/\/doi.org\/10.1038\/srep46920","order":10,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"44685"}}