{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:16:33Z","timestamp":1792451793846,"version":"4.5.0"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7222296"],"award-info":[{"award-number":["7222296"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:italic>Coicis<\/jats:italic><jats:italic>Semen<\/jats:italic> is an important food product and traditional Chinese medicine (TCM) derived from the dried and mature seeds of <jats:italic>Coix lacryma-jobi L.<\/jats:italic>var.<jats:italic>ma-yuen<\/jats:italic> (Roman.) Stapf. An increasing number of studies have investigated its use, either alone or in combination with other botanical drugs, to treat female reproductive system malignancies, and its pharmacological effects have been confirmed clinically. This review aims to provide an overview of <jats:italic>Coicis Semen<\/jats:italic>\u2019s historical role in treating female reproductive system malignancies based on TCM theory, to summarize clinical trials results, and to analyze information pertaining to the main phytochemical components, pharmacokinetics, related anti-cancer pharmacological effects, and toxicology of <jats:italic>Coicis Semen<\/jats:italic>. Information on <jats:italic>Coicis Semen<\/jats:italic> was collected from internationally accepted scientific databases. Seventy-four clinical trials were identified that used <jats:italic>Coicis Semen<\/jats:italic> in combination with other Chinese medicine to treat female reproductive system malignancies, most of which demonstrated good anti-tumor efficacy and few adverse reactions. To date, more than 80 individual compounds have been isolated from this botanical drug. In terms of anti-tumor effects, Coix seed oil has been studied the most. Pharmacokinetic data suggest that the active ingredients in <jats:italic>Coicis Semen<\/jats:italic> are widely distributed after administration, and <jats:italic>Coicis Semen<\/jats:italic> and its active compounds play a beneficial role in treating female reproductive system malignancies. Mechanistically, the anti-cancer effects may be related to inhibition of tumor cell proliferation and promotion of apoptosis, inhibition of tumor angiogenesis, suppression of the chronic inflammatory microenvironment of tumors, modulation of immune function, and regulation of the female reproductive system. Most acute toxicity and genotoxicity studies have shown that <jats:italic>Coicis Semen<\/jats:italic> is non-toxic. However, the existing studies have many limitations, and the future research direction should emphasize 1) the relationship between drug concentration and pharmacological action as well as toxicity; 2) the structural modification or the synthesis of analogues led by the active ingredients of <jats:italic>Coicis Semen<\/jats:italic> to enhance pharmacological activities and bioavailability; 3) accurately revealing the anti-cancer pharmacological effects of <jats:italic>Coicis Semen<\/jats:italic> and its compounds through multi-omics technology. We hope that this review can determine future directions and inform novel drug development for treating female reproductive malignancies.<\/jats:p>","DOI":"10.3389\/fphar.2023.1129874","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T10:20:06Z","timestamp":1677147606000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Coicis Semen for the treatment of malignant tumors of the female reproductive system: A review of traditional Chinese medicinal uses, phytochemistry, pharmacokinetics, and pharmacodynamics"],"prefix":"10.3389","volume":"14","author":[{"given":"Xue","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanlong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1590\/1806-9282.20210318","article-title":"Comparison of nonspecific inflammatory markers in endometrial cancer and hyperplasia","volume":"67","author":"Alper","year":"2021","journal-title":"Rev. Assoc. Med. Bras."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.1080\/14786419.2017.1292270","article-title":"Melanogenesis inhibitors from Coix lacryma-jobi seeds in B16-F10 melanoma cells","volume":"31","author":"Amen","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"100645","DOI":"10.1016\/j.drup.2019.100645","article-title":"The multi-factorial nature of clinical multidrug resistance in cancer","volume":"46","author":"Assaraf","year":"2019","journal-title":"Drug Resist Updat"},{"key":"B4","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.ygyno.2009.10.077","article-title":"ABC transporter gene expression in benign and malignant ovarian tissue","volume":"117","author":"Auner","year":"2010","journal-title":"Gynecol. Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.3390\/antiox10101583","article-title":"ER-mitochondria calcium flux by \u03b2-sitosterol promotes cell death in ovarian cancer","volume":"10","author":"Bae","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1021\/acs.jafc.8b04879","article-title":"Development of oral delivery systems with enhanced antioxidant and anticancer activity: Coix seed oil and \u03b2-carotene coloaded liposomes","volume":"67","author":"Bai","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1089\/jmf.2011.1780","article-title":"\u03b2-sitosterol prevents lipid peroxidation and improves antioxidant status and histoarchitecture in rats with 1,2-dimethylhydrazine-induced colon cancer","volume":"15","author":"Baskar","year":"2012","journal-title":"J. Med. Food"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e2001030","DOI":"10.1002\/cbdv.202001030","article-title":"Natural triterpenoids isolated from Akebia trifoliata stem explants exert a hypoglycemic effect via \u03b1-glucosidase inhibition and glucose uptake stimulation in insulin-resistant HepG2 cells","volume":"18","author":"Bian","year":"2021","journal-title":"Chem. Biodivers."},{"key":"B9","doi-asserted-by":"publisher","first-page":"6735","DOI":"10.2174\/0929867325666180607093111","article-title":"Phytosterols in cancer: From molecular mechanisms to preventive and therapeutic potentials","volume":"26","author":"Blanco-Vaca","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.phymed.2018.03.056","article-title":"Hexane fraction of adlay (Coix lachryma-jobi L.) testa ethanolic extract inhibits human uterine sarcoma cancer cells growth and chemosensitizes human uterine sarcoma cells to doxorubicin","volume":"47","author":"Chang","year":"2018","journal-title":"Phytomedicine"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3656","DOI":"10.1021\/jf021142a","article-title":"Antiproliferative and chemopreventive effects of adlay seed on lung cancer in vitro and in vivo","volume":"51","author":"Chang","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"113388","DOI":"10.1016\/j.jep.2020.113388","article-title":"Kanglaite enhances the efficacy of cisplatin in suppression of hepatocellular carcinoma via inhibiting CKLF1 mediated NF-\u03baB pathway and regulating transporter mediated drug efflux","volume":"264","author":"Chen","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.ijbiomac.2019.08.018","article-title":"Preparation, characterization and anti-diabetic activity of polysaccharides from adlay seed","volume":"139","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s10522-020-09857-z","article-title":"Coix seed oil prolongs lifespan and enhances stress resistance in Caenorhabditis elegans","volume":"21","author":"Chen","year":"2020","journal-title":"Biogerontology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.3390\/molecules27133984","article-title":"Adlay seed (Coix lacryma-jobi L. var. Ma-yuen Stapf.) ethanolic extract fractions and subfractions induce cell cycle arrest and apoptosis in human breast and cervical cancer cell lines","volume":"27","author":"Chiang","year":"2022","journal-title":"Molecules"},{"key":"B16","doi-asserted-by":"publisher","first-page":"995","DOI":"10.3109\/13880209.2014.952833","article-title":"Effect of kanglaite on rat cytochrome P450","volume":"53","author":"Du","year":"2015","journal-title":"Pharm. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s10495-021-01684-y","article-title":"Terpenoids' anti-cancer effects: Focus on autophagy","volume":"26","author":"El-Baba","year":"2021","journal-title":"Apoptosis"},{"key":"B18","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3969\/j.issn.1002-3429.2022.04.024","article-title":"Effects of different concentrations of Coix seed extract on proliferation, migration and invasion of oral squamous cell carcinoma cells and its mechanism","volume":"35","author":"Fan","year":"2022","journal-title":"Clin. Misdiagn. Misther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"178","DOI":"10.19428\/j.cnki.sjpm.2000.04.016","article-title":"Toxicity study and safety evaluation of Coix seed oil","volume":"4","author":"Fan","year":"2000","journal-title":"Shanghai J. Prev. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"529962","DOI":"10.3389\/fphar.2020.529962","article-title":"Coix seed oil exerts an anti-triple-negative breast cancer effect by disrupting miR-205\/S1PR1 axis","volume":"11","author":"Fang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3971\/j.issn.1000-8578.2004.04.015","article-title":"Experimental study on inhibiting angiogenesis in mice S180 sarcoma by Coix Lacryma-jobi injection","volume":"4","author":"Feng","year":"2004","journal-title":"Cancer Res. Prev. Treat."},{"key":"B22","doi-asserted-by":"publisher","first-page":"120533","DOI":"10.1016\/j.ijpharm.2021.120533","article-title":"Multicomponent thermosensitive lipid complexes enhance desmoplastic tumor therapy through boosting anti-angiogenesis and synergistic strategy","volume":"601","author":"Guo","year":"2021","journal-title":"Int. J. Pharm."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4826","DOI":"10.1021\/acs.molpharmaceut.9b00717","article-title":"Transferrin-functionalized microemulsions coloaded with Coix seed oil and tripterine deeply penetrate to improve cervical cancer therapy","volume":"16","author":"Guo","year":"2019","journal-title":"Mol. Pharm."},{"key":"B24","first-page":"3045","article-title":"Sex steroids and cervical cancer","volume":"32","author":"Hellberg","year":"2012","journal-title":"Anticancer Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/BF02171052","article-title":"Chinese medicine, Coix seeds increase peripheral cytotoxic T and NK cells","volume":"5","author":"Hidaka","year":"1992","journal-title":"Biotherapy"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.phymed.2018.03.010","article-title":"Exploring lipid markers of the quality of coix seeds with different geographical origins using supercritical fluid chromatography mass spectrometry and chemometrics","volume":"45","author":"Hou","year":"2018","journal-title":"Phytomedicine"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.3181\/0612-RM-306","article-title":"Effects of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) hull extracts on the secretion of progesterone and estradiol in vivo and in vitro","volume":"232","author":"Hsia","year":"2007","journal-title":"Exp. Biol. Med. (Maywood)."},{"key":"B28","doi-asserted-by":"publisher","first-page":"334","DOI":"10.13471\/j.cnki.j.sun.yat-sen.univ(med.sci).2000.0124","article-title":"The sensitizing enhancement effect of Coixenolide on the irradiation to human nasopharyngeal carcinoma CNE-2Z","volume":"5","author":"Hu","year":"2000","journal-title":"J. Sun Yat-sen Univ. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"131636","DOI":"10.1016\/j.foodchem.2021.131636","article-title":"Ultrasonic-assisted extraction of polysaccharides from coix seeds: Optimization, purification, and in vitro digestibility","volume":"374","author":"Hu","year":"2022","journal-title":"Food Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1021\/jf803255p","article-title":"Effect of Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) Testa and its phenolic components on Cu2+-treated low-density lipoprotein (LDL) oxidation and lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages","volume":"57","author":"Huang","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"40","DOI":"10.11669\/cpj.2016.01.010","article-title":"Bioavailability and pharmacokinetics of nanoparticles of Coix seed oil","volume":"51","author":"Huang","year":"2016","journal-title":"Chin. Pharm. J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.3892\/mmr.2014.2479","article-title":"Kanglaite stimulates anticancer immune responses and inhibits HepG2 cell transplantation-induced tumor growth","volume":"10","author":"Huang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"153154","DOI":"10.1016\/j.phymed.2019.153154","article-title":"Kanglaite injection plus platinum-based chemotherapy for stage III\/IV non-small cell lung cancer: A meta-analysis of 27 RCTs","volume":"67","author":"Huang","year":"2020","journal-title":"Phytomedicine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"61","DOI":"10.12166\/j.zgyz.1003-7969\/2020.08.013","article-title":"Acute toxicity and subacute toxicity of coix seed oil soft capsule","volume":"45","author":"Huang","year":"2020","journal-title":"China Oils Fats"},{"key":"B35","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3969\/j.issn.1002-1310.2016.05.002","article-title":"Clinical observation of coix seed in the treatment of flat warts","volume":"38","author":"Huang","year":"2016","journal-title":"Dermatol. Venereol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.3390\/molecules26071966","article-title":"Adlay Testa (Coix lachryma-jobi L. Var. Ma-yuen Stapf.) ethanolic extract and its active components exert anti-proliferative effects on endometrial cancer cells via cell cycle arrest","volume":"26","author":"Huang","year":"","journal-title":"Molecules"},{"key":"B37","doi-asserted-by":"publisher","first-page":"887","DOI":"10.3390\/biom11060887","article-title":"Ethanolic extracts of adlay testa and hull and their active biomolecules exert relaxing effect on uterine muscle contraction through blocking extracellular calcium influx in ex vivo and in vivo studies","volume":"11","author":"Huang","year":"","journal-title":"Biomolecules"},{"key":"B38","doi-asserted-by":"publisher","first-page":"7333","DOI":"10.1021\/jf0340512","article-title":"Methanolic extract of adlay seed suppresses COX-2 expression of human lung cancer cells via inhibition of gene transcription","volume":"51","author":"Hung","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"B39","first-page":"179","article-title":"Effect of coix seed on the changes in peripheral lymphocyte subsets","volume":"40","author":"Kaneda","year":"1992","journal-title":"Rinsho Byori"},{"key":"B40","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.ijpharm.2017.09.060","article-title":"Co-delivery strategies to overcome multidrug resistance in ovarian cancer","volume":"533","author":"Khan","year":"2017","journal-title":"Int. J. Pharm."},{"key":"B41","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1210\/er.2012-1043","article-title":"Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer","volume":"34","author":"Kim","year":"2013","journal-title":"Endocr. Rev."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1016\/j.fct.2008.01.033","article-title":"Isolation and characterization of new lactam compounds that inhibit lung and colon cancer cells from adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) bran","volume":"46","author":"Lee","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1042\/EBC20200175","article-title":"Functional roles of female sex hormones and their nuclear receptors in cervical cancer","volume":"65","author":"Lee","year":"2021","journal-title":"Essays Biochem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3969\/j.issn.1673-1727.2005.02.005","article-title":"Experimental study on pharmacokinetics and bioavailability of Coix seed oil preparations","volume":"2","author":"Li","year":"2005","journal-title":"China J. Tradit. Chin. Med. Pharm."},{"key":"B45","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3892\/or.2021.8174","article-title":"Hormone therapy for ovarian cancer: Emphasis on mechanisms and applications (Review)","volume":"46","author":"Li","year":"2021","journal-title":"Oncol. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"113890","DOI":"10.1016\/j.bcp.2020.113890","article-title":"Epigenetics\/epigenomics of triterpenoids in cancer prevention and in health","volume":"175","author":"Li","year":"","journal-title":"Biochem. Pharmacol."},{"key":"B47","first-page":"84","article-title":"Extraction of coix seed polysaccharide and its antioxidant activity","volume":"33","author":"Li","year":"2012","journal-title":"Food Res. Dev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"5645","DOI":"10.7501\/j,issn.0253-2670.2020.21.031","article-title":"Research progress on chemical constituents and pharmacological effects of Coicis Semen","volume":"51","author":"Li","year":"","journal-title":"Chin. Tradit. Herb. Drugs."},{"key":"B49","doi-asserted-by":"publisher","first-page":"4626","DOI":"10.3390\/molecules27144626","article-title":"Molecular action mechanism of coixol from soft-shelled adlay on tyrosinase: The future of cosmetics","volume":"27","author":"Lin","year":"2022","journal-title":"Molecules"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.3390\/molecules24081556","article-title":"Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) hull extract and active compounds inhibit proliferation of primary human leiomyoma cells and protect against sexual hormone-induced mice smooth muscle hyperproliferation","volume":"24","author":"Lin","year":"2019","journal-title":"Molecules"},{"key":"B51","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.13417\/j.gab.037.003587","article-title":"[Effect of coixenolide on proliferation and apoptosis of homologous nasopharyngeal carcinoma cells with different radioresistance","volume":"37","author":"Liu","year":"","journal-title":"Genomics Appl. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.7501\/j.issn.0253-2670.2015.18.006","article-title":"Study on preparation of butyryl galactose ester-modified coix component microemulsions and their anticancer activity in vitro","volume":"46","author":"Liu","year":"2015","journal-title":"Chin. Tradit. Herb. Drugs."},{"key":"B53","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.jchromb.2016.02.011","article-title":"Chemometrics applied to quality control and metabolomics for traditional Chinese medicines","author":"Liu","year":"2016","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.3390\/molecules23051042","article-title":"Antidiabetic effect of Cyclocarya paliurus leaves depends on the contents of antihyperglycemic flavonoids and antihyperlipidemic triterpenoids","volume":"23","author":"Liu","year":"","journal-title":"Molecules"},{"key":"B55","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/j.bbrc.2012.11.058","article-title":"A polysaccharide fraction of adlay seed (Coix lachryma-jobi L.) induces apoptosis in human non-small cell lung cancer A549 cells","volume":"430","author":"Lu","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B56","doi-asserted-by":"publisher","first-page":"309","DOI":"10.3892\/mmr.2016.5985","article-title":"Molecular inhibition mechanisms of cell migration and invasion by coix polysaccharides in A549 NSCLC cells via targeting S100A4","volume":"15","author":"Luo","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B57","first-page":"5666","article-title":"[Process of application history and modern research of coix seed","volume":"33","author":"Luo","year":"2018","journal-title":"China J. Tradit. Chin. Med. Pharm."},{"key":"B58","doi-asserted-by":"publisher","first-page":"20","DOI":"10.16429\/j.1009-7848.2013.06.010","article-title":"Immunomodulatory effect of Coix seed active polysaccharide on rats","volume":"13","author":"Lv","year":"2013","journal-title":"J. Chin. Inst. Food Sci. Technol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cyto.2012.01.015","article-title":"Inflammation and ovarian cancer","volume":"58","author":"Macci\u00f2","year":"2012","journal-title":"Cytokine"},{"key":"B60","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41572-021-00324-8","article-title":"Endometrial cancer","volume":"7","author":"Makker","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B61","doi-asserted-by":"publisher","first-page":"351","DOI":"10.5650\/jos.ess18255","article-title":"Potent in vitro anti-mouth cancer (KB) and immunostimulating activities of the Job's Tears (Coix lachryma-jobi Linn.) seed semi-purified extract cocktails containing linoleic acid","volume":"68","author":"Manosroi","year":"2019","journal-title":"J. Oleo. Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/ijc.32688","article-title":"Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: A review","volume":"146","author":"Nahand","year":"2020","journal-title":"Int. J. Cancer."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2833","DOI":"10.3390\/foods10112833","article-title":"Anti-cancer properties of coix seed oil against HT-29 colon cells through regulation of the PI3K\/AKT signaling pathway","volume":"10","author":"Ni","year":"2021","journal-title":"Foods"},{"key":"B64","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.jep.2012.07.025","article-title":"Antitumor activity and immunomodulatory effects of the intraperitoneal administration of Kanglaite in vivo in Lewis lung carcinoma","volume":"143","author":"Pan","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.carbpol.2018.04.100","article-title":"Dose matters: Direct killing or immunoregulatory effects of natural polysaccharides in cancer treatment","volume":"195","author":"Pang","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"B66","doi-asserted-by":"publisher","first-page":"5250","DOI":"10.3390\/ijms20215250","article-title":"Coix seed extract enhances the anti-pancreatic cancer efficacy of gemcitabine through regulating ABCB1- and ABCG2-mediated drug efflux: A bioluminescent pharmacokinetic and pharmacodynamic study","volume":"20","author":"Qian","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B67","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ijpharm.2016.03.001","article-title":"Bitargeted microemulsions based on coix seed ingredients for enhanced hepatic tumor delivery and synergistic therapy","volume":"503","author":"Qu","year":"2016","journal-title":"Int. J. Pharm."},{"key":"B68","doi-asserted-by":"publisher","first-page":"689","DOI":"10.5740\/jaoacint.18-0301","article-title":"Considerations for the quality control of newly registered traditional Chinese medicine in China: A review","volume":"102","author":"Qu","year":"2019","journal-title":"J. AOAC Int."},{"key":"B69","doi-asserted-by":"publisher","first-page":"114","DOI":"10.24920\/21806","article-title":"Relationship between traditional Chinese medicine(TCM)constitution and TCM syndrome in the diagnosis and treatment of chronic diseases","volume":"33","author":"Sang","year":"2018","journal-title":"Chin. Med. Sci. J."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.3781\/j.issn.1000-7431.2013.12.003","article-title":"The effect of Kanglaite injection in combination with gefitinib on angiogenesis in mice with Lewis lung cancer","volume":"33","author":"Shen","year":"2013","journal-title":"Tumor"},{"key":"B71","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.3969\/j.issn.1008-0805.2015.09.032","article-title":"Effects of different processing methods on the content of triolein, an anti-tumor component of Coix seed","volume":"26","author":"Shen","year":"2015","journal-title":"Lishizhen Med. Mater. Med. Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.1002\/cncr.30667","article-title":"Cervical cancer: A global health crisis","volume":"123","author":"Small","year":"2017","journal-title":"Cancer"},{"key":"B73","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1186\/s12906-017-1990-y","article-title":"Coix lacryma-jobi var. ma-yuen Stapf sprout extract has anti-metastatic activity in colon cancer cells in vitro","volume":"17","author":"Son","year":"2017","journal-title":"BMC Complement. Altern. Med."},{"key":"B74","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.soncn.2019.02.001","article-title":"Ovarian cancer: An integrated review","volume":"35","author":"Stewart","year":"2019","journal-title":"Semin. Oncol. Nurs."},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.26402\/jpp.2021.3.07","article-title":"The effects of gastric cancer interstitial fluid on tumors based on traditional Chinese medicine \u2018phlegm\u2019 theory and the investigation on the mechanism through microRNA-21 regulation","volume":"72","author":"Sun","year":"2021","journal-title":"J. Physiol. Pharmacol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7619\/jcmp.201908001","article-title":"Experimental study on apoptosis of gastric cancer cell line SGC-7901 induced by coix seed oil","volume":"23","author":"Sun","year":"2019","journal-title":"J. Clin. Med. Pract."},{"key":"B77","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B78","doi-asserted-by":"publisher","first-page":"39","DOI":"10.13194\/j.jlunivtcm.2013.03.41.taoxj.072","article-title":"Experimental study of acute toxicity and irritation of Coix seed oil","volume":"15","author":"Tao","year":"2013","journal-title":"J. Liaoning Univ. Tradit. Chin. Med."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1080\/15287390590967504","article-title":"The abortifacient effects from the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf","volume":"68","author":"Tzeng","year":"2005","journal-title":"J. Toxicol. Environ. Health A."},{"key":"B80","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1248\/cpb.9.43","article-title":"Studies on the antitumor components in the seeds of Coix lachryma-jobi L. var. ma-yuen (Roman) Stapf I: Isolation and antitumor activity of coixenolide","volume":"9","author":"Ukita","year":"1961","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"B81","first-page":"6414","article-title":"[in vitro and in vivo study of coixan improving cellular immune function by regulating the JAK3\/STAT5 pathway","volume":"36","author":"Wang","year":"2021","journal-title":"China J. Tradit. Chin. Med. Pharm."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1038\/s41598-017-01480-2","article-title":"Kanglaite sensitizes colorectal cancer cells to Taxol via NF-\u03ba\u0392 inhibition and connexin 43 upregulation","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"166","DOI":"10.5491\/SHAW.2012.3.3.166","article-title":"Malignant tumors of the female reproductive system","volume":"3","author":"Weiderpass","year":"2012","journal-title":"Saf. Health Work."},{"key":"B84","doi-asserted-by":"publisher","first-page":"8586596","DOI":"10.1155\/2020\/8586596","article-title":"Kanglaite injection combined with chemotherapy versus chemotherapy alone for the improvement of clinical efficacy and immune function in patients with advanced non-small-cell lung cancer: A systematic review and meta-analysis","volume":"2020","author":"Wen","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B85","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.4161\/cbt.6.12.5168","article-title":"Coix seed extract, a commonly used treatment for cancer in China, inhibits NFkappaB and protein kinase C signaling","volume":"6","author":"Woo","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"B86","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1002\/med.21708","article-title":"Recent advances in natural anti-HIV triterpenoids and analogs","volume":"40","author":"Wu","year":"2020","journal-title":"Med. Res. Rev."},{"key":"B87","doi-asserted-by":"publisher","first-page":"110717","DOI":"10.1016\/j.foodres.2021.110717","article-title":"Coix seed polysaccharides alleviate type 2 diabetes mellitus via gut microbiota-derived short-chain fatty acids activation of IGF1\/PI3K\/AKT signaling","volume":"150","author":"Xia","year":"2021","journal-title":"Food Res. Int."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.3321\/j.issn:1001-5302.2005.18.014","article-title":"Identification of triacylglycerols in coix oil by high performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry","volume":"30","author":"Xiang","year":"2005","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B89","first-page":"678","article-title":"Acute toxicity and genetic toxicity test of coixan","volume":"7","author":"Xiao","year":"2009","journal-title":"Cent. South Pharm."},{"key":"B90","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3969\/j.issn.1009-4393.2018.08.005","article-title":"The effect of coix seed oil on migration and invasion of laryngeal cancer","volume":"24","author":"Xiong","year":"2018","journal-title":"Contemp. Med."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.3969\/j.issn.1673-5293.2021.12.010","article-title":"Effect and mechanism of Coix seed oil on apoptosis in SKOV3 ovarian cancer cells","volume":"32","author":"Xu","year":"2021","journal-title":"Chin. J. Woman Child. Health Res."},{"key":"B92","doi-asserted-by":"publisher","first-page":"4227","DOI":"10.1002\/jsfa.8298","article-title":"Changes of the phenolic compounds and antioxidant activities in germinated adlay seeds","volume":"97","author":"Xu","year":"2017","journal-title":"J. Sci. Food Agric."},{"key":"B93","doi-asserted-by":"publisher","first-page":"5897","DOI":"10.1007\/s11033-022-07371-8","article-title":"Coix seed oil regulates mitochondrial functional damage to induce apoptosis of human pancreatic cancer cells via the PTEN\/PI3K\/AKT signaling pathway","volume":"49","author":"Yang","year":"","journal-title":"Mol. Biol. Rep."},{"key":"B94","doi-asserted-by":"publisher","first-page":"921255","DOI":"10.3389\/fnut.2022.921255","article-title":"Coix seed-based milk fermented with Limosilactobacillus reuteri improves lipid metabolism and gut microbiota in mice fed with a high-fat diet","volume":"9","author":"Yang","year":"","journal-title":"Front. Nutr."},{"key":"B95","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.3390\/nu11102473","article-title":"Food-drug interaction between the Adlay bran oil and drugs in rats","volume":"11","author":"Yao","year":"2019","journal-title":"Nutrients"},{"key":"B96","doi-asserted-by":"publisher","first-page":"126037","DOI":"10.1016\/j.foodchem.2019.126037","article-title":"Effects of fermentation with Lactobacillus plantarum NCU137 on nutritional, sensory and stability properties of Coix (Coix lachryma-jobi L.) seed","volume":"314","author":"Yin","year":"2020","journal-title":"Food Chem."},{"key":"B97","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3870\/j.issn.1672-0741.2016.04.015","article-title":"Effect of Coix seed oil on the vasculogenic mimicry formation of HCT116 cells","volume":"45","author":"Yu","year":"2016","journal-title":"Acta Med. Univ. Sci. Technol. huazhong."},{"key":"B98","doi-asserted-by":"publisher","first-page":"3284","DOI":"10.7501\/j.issn.0253-2670.2014.22.013","article-title":"Preparation of Lingyi Formula multicomponent microemulsions and its anti-lung cancer activity","volume":"45","author":"Yuan","year":"2014","journal-title":"Chin. Tradit. Herb. Drugs."},{"key":"B99","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1080\/13880209.2019.1687526","article-title":"Coix lachryma-jobi extract ameliorates inflammation and oxidative stress in a complete Freund's adjuvant-induced rheumatoid arthritis model","volume":"57","author":"Zhang","year":"","journal-title":"Pharm. Biol."},{"key":"B100","first-page":"11","article-title":"The immunoregulatory effect of triglyceride in Coicis Semen combined with Sigirone in advanced pancreatic cancer","volume":"16","author":"Zhang","year":"2017","journal-title":"Health Way"},{"key":"B101","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s00520-018-4313-z","article-title":"The effect of a coix seed oil injection on cancer pain relief","volume":"27","author":"Zhang","year":"","journal-title":"Support. Care Cancer"},{"key":"B102","doi-asserted-by":"publisher","first-page":"410979","DOI":"10.1155\/2015\/410979","article-title":"Classic and modern meridian studies: A review of low hydraulic resistance channels along meridians and their relevance for therapeutic effects in traditional Chinese medicine","volume":"2015","author":"Zhang","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"B103","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.19540\/j.cnki.cjcmm.20211228.601","article-title":"Research status and prospects of integration of habitat processing and processing of Chinese medicinal decoction pieces","volume":"47","author":"Zhang","year":"2022","journal-title":"China J. Chin. Mater. Medica"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.3892\/etm.2017.4650","article-title":"Kanglaite inhibits the expression of drug resistance genes through suppressing PVT1 in cisplatin-resistant gastric cancer cells","volume":"14","author":"Zhang","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"B105","doi-asserted-by":"publisher","first-page":"13","DOI":"10.16662\/j.cnki.1674-0742.2020.16.013","article-title":"Effect of paclitaxel combined with carboplatin on angiogenesis and invasive ability in patients with cervical cancer","volume":"39","author":"Zhang","year":"2020","journal-title":"China Foreign Med. Treat."},{"key":"B106","doi-asserted-by":"publisher","first-page":"60","DOI":"10.16809\/j.cnki.2096-3653.2019092409","article-title":"Effects of fried coix seed oil on apoptosis of MCF-7 and ZR-75-1 cells and its related oxidative stress mechanism","volume":"36","author":"Zheng","year":"2020","journal-title":"J. Guangdong Pharm. Univ."},{"key":"B107","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3390\/nu14010123","article-title":"Coix seed diet ameliorates immune function disorders in experimental colitis mice","volume":"14","author":"Zhou","year":"2021","journal-title":"Nutrients"},{"key":"B108","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.19540\/j.cnki.cjcmm.20200328.306","article-title":"Historical evolution of Coicis Semen processing methods","volume":"45","author":"Zhou","year":"2020","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B109","doi-asserted-by":"publisher","first-page":"84","DOI":"10.16438\/j.0513-4870.2017-0782","article-title":"Impact of Coix seed oil on fluorescence excretion pharmacokinetics and protein expression in doxorubicin-resistant cells MCF-7\/DOX","volume":"53","author":"Zhu","year":"2018","journal-title":"Acta Pharm. Sin."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1129874\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T10:20:34Z","timestamp":1677147634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1129874\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,23]]},"references-count":109,"alternative-id":["10.3389\/fphar.2023.1129874"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1129874","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,23]]},"article-number":"1129874"}}