{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:52:52Z","timestamp":1792979572993,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hormone-associated cancers use steroid metabolism to grow and avoid the immune system, while traditional treatments have to deal with drug resistance and systemic toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study is mainly divided into two parts. First, screening natural active ingredients for anti-lung cancer and anti-liver cancer and their network pharmacology research. Second, target identification and clinical drug design of potential medicinal components focusing on hormone metabolic pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>\n                      We found that ergosterol and quercetagetin are dual-targeting phytochemicals that interfered with hormone metabolism in a potential contributing pathway through androgen receptor (AR) and estrogen receptor 1 (ESR1) and enzymes such as 3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      HSD\/17\n                      <jats:italic>\u03b2<\/jats:italic>\n                      HSD using network pharmacology, molecular docking, and SMRT sequencing. We used HepG2 and A549 cell lines to do mechanistic studies. Our\n                      <jats:italic>in vivo<\/jats:italic>\n                      results were confirmed by mouse models of Lewis lung carcinoma and H22 hepatoma. Ergosterol may stop 3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -hydroxysteroid dehydrogenase (3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      HSD) from working, which stop the conversion of DHEA to androstenedione in HepG2 cells. Quercetagetin may affect 17\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -hydroxysteroid dehydrogenase (17\n                      <jats:italic>\u03b2<\/jats:italic>\n                      HSD), which throw off the balance of estradiol and estrone in A549 cells.\n                      <jats:italic>In vivo<\/jats:italic>\n                      studies showed that quercetagetin significantly stopped splenomegaly and thymic atrophy (p &amp;lt; 0.001). Pharmacokinetic analysis showed that 8 out of 31 compounds met Lipinski\u2019s criteria. ADMET testing showed that ergosterol had poor solubility (Log S = \u22126.91) and fully bound to plasma proteins. Quercetagetin didn't pass through membranes well and was sensitive to P-glycoprotein efflux. Tailored nanocarrier systems showed significant improvements in overcoming these limitations: Ergosterol\u2019s solubility increased by 1,000 times, and quercetagetin\u2019s P-gp substrate status was removed. Molecular dynamics simulations showed that drug-nanocarrier interactions were stable, with ergosterol showing very little change (RMSD &amp;lt;0.1\u00a0nm). Overall, these findings support a working mechanistic hypothesis and motivate nanodelivery strategies to improve the developability of these phytochemicals for further preclinical evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1773130","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:37:15Z","timestamp":1777613835000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Dual-targeting phytochemicals Ergosterol and Quercetagetin implicate steroid metabolism\u2013associated pathways in lung and liver cancer models"],"prefix":"10.3389","volume":"17","author":[{"given":"Yujiao","family":"Chen","sequence":"first","affiliation":[{"name":"Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"Department of Physiology, Department of Cardiology of the Second Affiliated Hospital and School of Basic Medical 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