{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:51:21Z","timestamp":1781772681414,"version":"3.54.5"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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>\n                      Tongue squamous cell carcinoma (TSCC) is a prevalent and aggressive oral malignancy with a poor prognosis and limited treatment options, underscoring the need for novel therapeutic agents. Tryptanthrin derivatives have shown promising anticancer potential across various cancers. This study aimed to evaluate the antitumor efficacy and elucidate the mechanism of action of a novel tryptanthrin derivative,\n                      <jats:bold>g2<\/jats:bold>\n                      , against TSCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The cytotoxic effect of\n                      <jats:bold>g2<\/jats:bold>\n                      was initially screened against CAL-27 and SCC9 TSCC cells using a CCK-8 assay among 36 derivatives. Its half-maximal inhibitory concentration (IC\n                      <jats:sub>50<\/jats:sub>\n                      ) was determined. A comprehensive set of\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays, including scratch wound-healing, Transwell migration, flow cytometry for apoptosis and cell cycle analysis, transcriptome sequencing, and western blotting, were employed to assess its effects on cell migration, apoptosis, cycle progression, and underlying signaling pathways. For\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation, a xenograft model was established by implanting CAL-27 cells into nude mice, which were then treated with\n                      <jats:bold>g2<\/jats:bold>\n                      (10 or 20\u00a0mg\/kg) via intratumoral injection. Tumor growth was monitored, and harvested tissues were analyzed by western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>\n                      <jats:bold>g2<\/jats:bold>\n                      demonstrated the most potent cytotoxicity, with IC\n                      <jats:sub>50<\/jats:sub>\n                      values of 1.997\u00a0\u03bcM for CAL-27 and 2.134\u00a0\u03bcM for SCC9 cells. It significantly inhibited cell migration and invasion, induced apoptosis, and caused S-phase cell cycle arrest in a dose-dependent manner. Transcriptome sequencing and western blotting analyses revealed that\n                      <jats:bold>g2<\/jats:bold>\n                      activated the PI3K\/AKT\/P53 signaling pathway, evidenced by the downregulation of PI3K\/AKT and upregulation of P53.\n                      <jats:italic>In vivo<\/jats:italic>\n                      ,\n                      <jats:bold>g2<\/jats:bold>\n                      treatment markedly suppressed tumor growth without observable systemic toxicity, and consistent modulation of the PI3K\/AKT\/P53 pathway was confirmed in tumor tissues. These findings collectively demonstrate that the tryptanthrin derivative\n                      <jats:bold>g2<\/jats:bold>\n                      exerts significant anti-TSCC effects both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      , primarily through the modulation of the PI3K\/AKT\/P53 pathway, highlighting its potential as a promising therapeutic candidate. Further studies are warranted to explore its full mechanistic spectrum and efficacy in broader models.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1789002","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:58:04Z","timestamp":1781769484000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The tryptanthrin derivative g2 suppresses tongue squamous cell carcinoma via PI3K\/AKT\/P53 cathway modulation: evidence from in vitro and in vivo studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Miao","sequence":"first","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng","family":"Li","sequence":"additional","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4522","DOI":"10.3390\/ijms24054522","article-title":"Drugging the PI3K\/AKT\/mTOR pathway in ER+ breast cancer","volume":"24","author":"Alves","year":"2023","journal-title":"Int. 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