{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:35:49Z","timestamp":1786977349729,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060666"],"award-info":[{"award-number":["82060666"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    : Liver cancer is an extremely common cancer with the highest mortality rate and poor prognosis. Owing to their low systemic toxicity and few side effects, natural compounds may provide better therapeutic effects for patients. (2\n                    <jats:italic>E<\/jats:italic>\n                    )\u20101\u2010(2,4,6\u2010trimethoxyphenyl)\u20103\u2010(4\u2010chlorophenyl)prop\u20102\u2010en\u20101\u2010one (\n                    <jats:italic>TMOCC<\/jats:italic>\n                    ), a chalcone derivative, exhibits cytotoxicity towards many tumor cells. However, the anticancer mechanism of\n                    <jats:italic>TMOCC<\/jats:italic>\n                    has not been elucidated in human hepatocellular carcinoma (\n                    <jats:italic>HCC<\/jats:italic>\n                    ).\n                    <jats:bold>Methods<\/jats:bold>\n                    : Cell Counting Kit\u20108 and colony formation assays were used to evaluate the effects of\n                    <jats:italic>TMOCC<\/jats:italic>\n                    on viability and proliferation. Mitochondrial transmembrane potential and flow cytometry assays were used to detect apoptosis. The expression levels of proteins related to apoptosis, the\n                    <jats:italic>RAS\u2010ERK<\/jats:italic>\n                    and\n                    <jats:italic>AKT\/FOXO3a<\/jats:italic>\n                    signaling pathways were assessed using western blot. Potential targets of\n                    <jats:italic>TMOCC<\/jats:italic>\n                    were detected using molecular docking analysis.\n                    <jats:bold>Results<\/jats:bold>\n                    :\n                    <jats:italic>TMOCC<\/jats:italic>\n                    inhibited viability and proliferation, and induced the loss of mitochondrial transmembrane potential, apoptosis and DNA double\u2010strand breaks in both\n                    <jats:italic>HCC<\/jats:italic>\n                    cells. The\n                    <jats:italic>RAS\u2010ERK<\/jats:italic>\n                    and\n                    <jats:italic>AKT\/FOXO3a<\/jats:italic>\n                    signaling pathways were suppressed by\n                    <jats:italic>TMOCC<\/jats:italic>\n                    . Finally,\n                    <jats:italic>ERK1<\/jats:italic>\n                    ,\n                    <jats:italic>PARP\u20101<\/jats:italic>\n                    , and\n                    <jats:italic>BAX<\/jats:italic>\n                    were identified as potential targets of\n                    <jats:italic>TMOCC<\/jats:italic>\n                    .\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : Taken together, our results show that\n                    <jats:italic>TMOCC<\/jats:italic>\n                    promotes apoptosis by suppressing the\n                    <jats:italic>RAS\u2010ERK<\/jats:italic>\n                    and\n                    <jats:italic>AKT\/FOXO3a<\/jats:italic>\n                    signaling pathways.\n                    <jats:italic>TMOCC<\/jats:italic>\n                    may be a potential multi\u2010target compound that is effective against liver cancer.\n                  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