{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T03:28:17Z","timestamp":1779161297253,"version":"3.51.4"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Tubeimoside I (TBMS1), also referred to as tubeimoside A, is a natural compound extracted from the plant Tu Bei Mu (<jats:italic>Bolbostemma paniculatum<\/jats:italic>), which is a traditional Chinese herb used to treat multiple diseases for more than 1,000 years. Studies in recent years reported its anti-tumor activity in several cancers. However, whether it is effective in melanoma remains unknown. In the current study, we discovered that TBMS1 treatment inhibited melanoma cell proliferation <jats:italic>in vitro<\/jats:italic> and tumorigenecity <jats:italic>in vivo<\/jats:italic>. Besides, we also observed that TBMS1 treatment induced a partly disrupted autophagy, which still remained a protective role, disruption of which by chloroquine (CQ) or 3-methyladenine (3-MA) enhanced TBMS1-induced cell proliferation inhibition. CQ combined with TBMS1 even induced cellular apoptosis. BRAF(V600E) mutation and its continuously activated downstream MEK1\/2-ERK1\/2 cascade are found in 50% of melanomas and are important for malanomagenesis. However, hyperactivating MEK1\/2-ERK1\/2 cascade can also inhibit tumor growth. Intriguingly, we observed that TBMS1 rapidly hyperactivated MEK1\/2-ERK1\/2, inhibition of which by its inhibitor SL-327 rescued the anti-cancerous effects of TBMS1. Besides, the targets of TBMS1 were predicted by the ZINC Database based on its structure. It is revealed that protein-tyrosine phosphatase 1B (PTP1B) might be one of the targets of TBMS1. Inhibition of PTP1B by its selective inhibitor TCS401 or shRNA rescued the anti-cancerous effects of TBMS1 in melanoma cells. These results indicated that TBMS1 might activate PTP1B, which further hyperactivates MEK1\/2-ERK1\/2 cascade, thereby inhibiting cell proliferation in melanoma. Our results provided the potentiality of TBMS1 as a drug candidate for melanoma therapy and confirmed that rapidly hyperactivating an oncogenic signaling pathway may also be a promising strategy for cancer treatment.<\/jats:p>","DOI":"10.3389\/fcell.2020.607757","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T21:36:26Z","timestamp":1610055386000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Tubeimoside I Inhibits Cell Proliferation and Induces a Partly Disrupted and Cytoprotective Autophagy Through Rapidly Hyperactivation of MEK1\/2-ERK1\/2 Cascade via Promoting PTP1B in Melanoma"],"prefix":"10.3389","volume":"8","author":[{"given":"Juan","family":"Du","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengqin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangzhao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaomin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjuan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"33939","DOI":"10.1074\/jbc.m605819200","article-title":"Activation of Ras up-regulates pro-apoptotic BNIP3 in nitric oxide-induced cell death.","volume":"281","author":"An","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4161\/15384101.2014.980700","article-title":"Targeted protein degradation as a tumor suppressor.","volume":"13","author":"Arat","year":"2014","journal-title":"Cell Cycle"},{"key":"B3","doi-asserted-by":"publisher","first-page":"18694","DOI":"10.18632\/oncotarget.7909","article-title":"Suppression of B-Raf(V600E) cancers by MAPK hyper-activation.","volume":"7","author":"Atiq","year":"2016","journal-title":"Oncotarget"},{"key":"B4","first-page":"12517","article-title":"Tubeimoside-1 inhibits the growth and invasion of colorectal cancer cells through the Wnt\/beta-catenin signaling pathway.","volume":"8","author":"Bian","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1097\/ppo.0000000000000234","article-title":"Intratumoral approaches for the treatment of melanoma.","volume":"23","author":"Bommareddy","year":"2017","journal-title":"Cancer J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1742-4658.2009.07366.x","article-title":"ERK and cell death: mechanisms of ERK-induced cell death\u2013apoptosis, autophagy and senescence.","volume":"277","author":"Cagnol","year":"2010","journal-title":"FEBS J."},{"key":"B7","first-page":"535","article-title":"Tubeimoside-1 induces G2\/M phase arrest and apoptosis in SKOV-3 cells through increase of intracellular Ca(2)(+) and caspase-dependent signaling pathways.","volume":"40","author":"Chen","year":"2012","journal-title":"Int. J. Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.bbrc.2008.09.018","article-title":"ERK and JNK mediate TNFalpha-induced p53 activation in apoptotic and autophagic L929 cell death.","volume":"376","author":"Cheng","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"6861","DOI":"10.1158\/0008-5472.can-05-3557","article-title":"Disruption of autophagy at the maturation step by the carcinogen lindane is associated with the sustained mitogen-activated protein kinase\/extracellular signal-regulated kinase activity.","volume":"66","author":"Corcelle","year":"2006","journal-title":"Cancer Res."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025139","article-title":"Oncogenic stress induced by acute hyper-activation of Bcr-Abl leads to cell death upon induction of excessive aerobic glycolysis.","volume":"6","author":"Dengler","year":"2011","journal-title":"PLoS One"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010004","article-title":"The autophagy-lysosomal pathways and their emerging roles in modulating proteostasis in tumors.","volume":"8","author":"Dong","year":"2018","journal-title":"Cells"},{"key":"B12","first-page":"728","article-title":"FOXO3a-SIRT6 axis suppresses aerobic glycolysis in melanoma.","volume":"56","author":"Dong","year":"2020","journal-title":"Intl. J. Oncol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.cellsig.2019.04.009","article-title":"Transcriptional activation of SIRT6 via FKHRL1\/FOXO3a inhibits the warburg effect in glioblastoma cells.","volume":"60","author":"Dong","year":"2019","journal-title":"Cell. Signal."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1073\/pnas.0304242101","article-title":"The role of protein tyrosine phosphatase 1B in Ras signaling.","volume":"101","author":"Dube","year":"2004","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B15","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-018-1151-3","article-title":"Tubeimoside I induces accumulation of impaired autophagolysosome against cervical cancer cells by both initiating autophagy and inhibiting lysosomal function.","volume":"9","author":"Feng","year":"2018","journal-title":"Cell Death Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"10.11.1","DOI":"10.1002\/0471142905.hg1011s57","article-title":"The catalogue of somatic mutations in cancer (COSMIC).","volume":"57","author":"Forbes","year":"2008","journal-title":"Curr. Protoc. Hum. Gene."},{"key":"B17","doi-asserted-by":"crossref","first-page":"446e","DOI":"10.1097\/01.prs.0000438448.78400.40","article-title":"Managing malignant melanoma.","volume":"133","author":"Gigliofiorito","year":"2014","journal-title":"Plast Reconstr. Surg."},{"key":"B18","doi-asserted-by":"crossref","first-page":"e720","DOI":"10.1016\/S1470-2045(18)30596-5","article-title":"Adjuvant melanoma therapy with new drugs: should physicians continue to focus on metastatic disease or use it earlier in primary melanoma?","volume":"19","author":"Grob","year":"2018","journal-title":"Lancet Oncol."},{"key":"B19","first-page":"12075","article-title":"Tubeimoside-1 (TBMS1) inhibits lung cancer cell growth and induces cells apoptosis through activation of MAPK-JNK pathway.","volume":"8","author":"Hao","year":"2015","journal-title":"Intl. J. Clin. Exp. Pathol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1016\/j.cellsig.2015.07.003","article-title":"ERK1\/2 can feedback-regulate cellular MEK1\/2 levels.","volume":"27","author":"Hong","year":"2015","journal-title":"Cell Signal."},{"key":"B21","doi-asserted-by":"publisher","first-page":"366","DOI":"10.3109\/08923973.2015.1063644","article-title":"Tubeimoside-1 inhibits the proliferation and activation of mouse T lymphocytes through signal transduction pathways.","volume":"37","author":"Huang","year":"2015","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1021\/ci049714%2B","article-title":"ZINC\u2013a free database of commercially available compounds for virtual screening.","volume":"45","author":"Irwin","year":"2005","journal-title":"J. Chem. Inform. Model."},{"key":"B23","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.ejmech.2018.11.001","article-title":"The potential role of tubeimosides in cancer prevention and treatment.","volume":"162","author":"Islam","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/s41401-018-0165-9","article-title":"Tubeimoside-1, a triterpenoid saponin, induces cytoprotective autophagy in human breast cancer cells in vitro via Akt-mediated pathway.","volume":"40","author":"Jiang","year":"2019","journal-title":"Acta Pharmacol. Sin."},{"key":"B25","doi-asserted-by":"crossref","first-page":"825","DOI":"10.5604\/01.3001.0010.4672","article-title":"The cell on the edge of life and death: crosstalk between autophagy and apoptosis.","volume":"71","author":"Kasprowska-Liskiewicz","year":"2017","journal-title":"Postepy Hig. Med. Dosw."},{"key":"B26","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.pharmthera.2018.02.007","article-title":"ERK1\/2 inhibitors: new weapons to inhibit the RAS-regulated RAF-MEK1\/2-ERK1\/2 pathway.","volume":"187","author":"Kidger","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"B27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"B28","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1158\/2159-8290.cd-13-0424","article-title":"A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors.","volume":"4","author":"Konieczkowski","year":"2014","journal-title":"Cancer Discov."},{"key":"B29","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/nrc1738","article-title":"Lysosomes and autophagy in cell death control.","volume":"5","author":"Kroemer","year":"2005","journal-title":"Nat. Rev. Cance"},{"key":"B30","doi-asserted-by":"publisher","first-page":"38078","DOI":"10.18632\/oncotarget.9348","article-title":"Derivatives of 6-cinnamamido-quinoline-4-carboxamide impair lysosome function and induce apoptosis.","volume":"7","author":"Kuo","year":"2016","journal-title":"Oncotarget"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.1007\/s00018-016-2297-8","article-title":"Negative feedback regulation of the ERK1\/2 MAPK pathway.","volume":"73","author":"Lake","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1177\/1203475418773360","article-title":"Brief report: increase in melanoma incidence in ontario.","volume":"22","author":"Langley","year":"2018","journal-title":"J. Cutan. Med. Surg."},{"key":"B33","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1016\/j.bbapap.2009.09.018","article-title":"The two faces of PTP1B in cancer.","volume":"1804","author":"Lessard","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"B34","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1158\/1541-7786.mcr-18-0327","article-title":"Hyperactivation of MAPK Signaling Is Deleterious to RAS\/RAF-mutant melanoma.","volume":"17","author":"Leung","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1007\/s00204-019-02433-6","article-title":"Ochratoxin a causes mitochondrial dysfunction, apoptotic and autophagic cell death and also induces mitochondrial biogenesis in human gastric epithelium cells.","volume":"93","author":"Li","year":"2019","journal-title":"Arch. Toxicol."},{"key":"B36","doi-asserted-by":"crossref","DOI":"10.1186\/s40880-017-0219-2","article-title":"Autophagy and multidrug resistance in cancer.","volume":"36","author":"Li","year":"2017","journal-title":"Chin. J. Cancer"},{"key":"B37","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.canlet.2015.01.020","article-title":"PTP1B promotes cell proliferation and metastasis through activating src and ERK1\/2 in non-small cell lung cancer.","volume":"359","author":"Liu","year":"2015","journal-title":"Cancer Lett."},{"key":"B38","doi-asserted-by":"publisher","first-page":"112354","DOI":"10.18632\/oncotarget.19379","article-title":"Inactivation\/deficiency of DHODH induces cell cycle arrest and programed cell death in melanoma.","volume":"8","author":"Liu","year":"2017","journal-title":"Oncotarget"},{"key":"B39","first-page":"63","article-title":"Improved glucose-stimulated insulin secretion by intra-islet inhibition of protein-tyrosine phosphatase 1B expression in rats fed a high-fat diet.","volume":"35","author":"Lu","year":"2012","journal-title":"J. Endocrinol. Invest."},{"key":"B40","doi-asserted-by":"publisher","first-page":"551","DOI":"10.2174\/1389450118666170222143739","article-title":"Recent advances in protein tyrosine phosphatase 1B targeted drug discovery for type II diabetes and obesity.","volume":"19","author":"Maheshwari","year":"2018","journal-title":"Curr. Drug Targets"},{"key":"B41","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nrm2239","article-title":"Self-eating and self-killing: crosstalk between autophagy and apoptosis.","volume":"8","author":"Maiuri","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11091299","article-title":"AT2 receptor mediated activation of the tyrosine phosphatase PTP1B blocks caveolin-1 enhanced migration, invasion and metastasis of cancer cells.","volume":"3","author":"Mart\u00ednez-Meza","year":"2019","journal-title":"Cancers"},{"key":"B43","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/annonc\/mdz054","article-title":"Targeting the MAPK pathway in advanced BRAF wild-type melanoma.","volume":"30","author":"Massa","year":"2019","journal-title":"Ann. Oncol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.1038\/onc.2011.160","article-title":"Raf kinases in cancer-roles and therapeutic opportunities.","volume":"30","author":"Maurer","year":"2011","journal-title":"Oncogene"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2614","DOI":"10.1002\/cncr.32817","article-title":"Use of immunotherapy and surgery for stage IV melanoma.","volume":"126","author":"Molina","year":"2020","journal-title":"Cancer"},{"key":"B46","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.ceb.2009.12.002","article-title":"Cytoprotective roles for autophagy.","volume":"22","author":"Moreau","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.cell.2009.05.023","article-title":"p62 at the crossroads of autophagy, apoptosis, and cancer.","volume":"137","author":"Moscat","year":"2009","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.tibs.2006.03.009","article-title":"MAPK signal specificity: the right place at the right time.","volume":"31","author":"Murphy","year":"2006","journal-title":"Trends Biochem. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.2147\/TCRM.S167579","article-title":"Effect of denosumab on bone mineral density in Japanese women with osteopenia treated with aromatase inhibitors for breast cancer: subgroup analyses of a Phase II study.","volume":"14","author":"Nakatsukasa","year":"2018","journal-title":"Ther. Clin. Risk Manag."},{"key":"B50","doi-asserted-by":"publisher","first-page":"39090","DOI":"10.1074\/jbc.M006198200","article-title":"Erk1\/2-dependent phosphorylation of Galpha-interacting protein stimulates its GTPase accelerating activity and autophagy in human colon cancer cells.","volume":"275","author":"Ogier-Denis","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s11515-014-1299-x","article-title":"Growth arrest signaling of the Raf\/MEK\/ERK pathway in cancer.","volume":"9","author":"Park","year":"2014","journal-title":"Front. Biol."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2019.104624","article-title":"PTP1B phosphatase as a novel target of oleuropein activity in MCF-7 breast cancer model.","volume":"61","author":"Przychodzen","year":"2019","journal-title":"Toxicol. Vitro."},{"key":"B53","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s40257-017-0325-6","article-title":"Advanced melanoma: current treatment options, biomarkers, and future perspectives.","volume":"19","author":"Rozeman","year":"2018","journal-title":"Am. J. Clin. Dermatol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/nrd2272","article-title":"Potential therapeutic applications of autophagy.","volume":"6","author":"Rubinsztein","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1002\/mc.23047","article-title":"Targeting ERK beyond the boundaries of the kinase active site in melanoma.","volume":"58","author":"Sammons","year":"2019","journal-title":"Mol. Carcinog."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061483","article-title":"Targeting the ERK signaling pathway in melanoma.","volume":"20","author":"Savoia","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.3892\/ol.2018.9051","article-title":"Tubeimoside-1 inhibits the proliferation and metastasis by promoting miR-126-5p expression in non-small cell lung cancer cells.","volume":"16","author":"Shi","year":"2018","journal-title":"Oncol. Lett."},{"key":"B58","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019.","volume":"69","author":"Siegel","year":"2019","journal-title":"Cancer J. Clin."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1016\/j.ejca.2012.11.019","article-title":"Resistance to BRAF-targeted therapy in melanoma.","volume":"49","author":"Sullivan","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"B60","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.bbrc.2014.11.038","article-title":"Inhibition of MEK\/ERK activation attenuates autophagy and potentiates pemetrexed-induced activity against HepG2 hepatocellular carcinoma cells.","volume":"456","author":"Tong","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33718.022","article-title":"Hyperactivation of ERK by multiple mechanisms is toxic to RTK-RAS mutation-driven lung adenocarcinoma cells.","volume":"7","author":"Unni","year":"2018","journal-title":"ELife"},{"key":"B62","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/ijc.2910480116","article-title":"Establishment and characterization of a human melanoma cell line (MV3) which is highly metastatic in nude mice.","volume":"48","author":"van Muijen","year":"1991","journal-title":"Intl. J. Cancer"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096801","article-title":"IHC Profiler: an open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples.","volume":"9","author":"Varghese","year":"2014","journal-title":"PLoS One"},{"key":"B64","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1017\/S0007114512000153","article-title":"Effect of a novel proteoglycan PTP1B inhibitor from Ganoderma lucidum on the amelioration of hyperglycaemia and dyslipidaemia in db\/db mice.","volume":"108","author":"Wang","year":"2012","journal-title":"Br. J. Nutr."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.2147\/OTT.S164503","article-title":"The effect of tubeimoside-1 on the proliferation, metastasis and apoptosis of oral squamous cell carcinoma in vitro.","volume":"11","author":"Wu","year":"2018","journal-title":"Onco Targets Ther."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-019-0778-y","article-title":"Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer.","volume":"11","author":"Yang","year":"2019","journal-title":"Clin. Epigenet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1055\/s-2006-959459","article-title":"Potent anti-tumor activity and low toxicity of tubeimoside 1 isolated from Bolbostemma paniculatum.","volume":"60","author":"Yu","year":"1994","journal-title":"Planta Med."},{"key":"B68","first-page":"463","article-title":"Structure-activity relationship of tubeimosides in anti-inflammatory, antitumor, and antitumor-promoting effects.","volume":"22","author":"Yu","year":"2001","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.607757\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T07:25:50Z","timestamp":1610263550000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.607757\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,17]]},"references-count":68,"alternative-id":["10.3389\/fcell.2020.607757"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2020.607757","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,17]]},"article-number":"607757"}}