{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:24:12Z","timestamp":1788265452446,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and the third leading cause of cancer\u2010related deaths worldwide, with high mortality and limited clinical treatment options. In this study, we identified hypericin as a potent inducer of HCC cell death by screening traditional Chinese Medicine Monomer Library screening. Hypericin, a natural photosensitizer derived from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Hypericum perforatum<\/jats:italic>\n                    <\/jats:styled-content>\n                    , significantly inhibited the proliferation, migration, and colony formation of HCC cell lines, and induced apoptosis in\u00a0vitro. In\u00a0vivo, hypericin effectively suppressed tumor growth in Hepa1\u20106 subcutaneous tumor and AKT\/c\u2010Myc\u2010driven orthotopic mouse HCC models. Flow cytometry analysis revealed that hypericin treatment increased the CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell proportion and activity within the tumor microenvironment. Combination therapy with hypericin and anti\u2010PD\u2010L1 antibody resulted in significant tumor growth inhibition and prolonged survival. Mechanistically, hypericin promoted the interaction between AKT and HSPA5, leading to autophagic degradation of AKT. This process inhibited the AKT\/mTOR\/S6 signaling pathway, downregulated the expression of downstream anti\u2010apoptotic proteins MCL\u20101 and XIAP, and triggered mitochondria\u2010mediated apoptosis in HCC cells.\n                  <\/jats:p>","DOI":"10.1111\/cas.70453","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T02:49:46Z","timestamp":1783046986000},"page":"2567-2585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypericin Suppresses Liver Cancer Through Autophagic Degradation of\n                    <scp>AKT<\/scp>\n                    and Eliciting Antitumor Immune Response"],"prefix":"10.1111","volume":"117","author":[{"given":"Sien","family":"Ma","sequence":"first","affiliation":[{"name":"School of Pharmacy Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui University of Chinese Medicine  Hefei Anhui 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