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Drug\u2010induced cellular senescence provides a permanent cell cycle arrest during tumorigenesis and cancer development, particularly when combined with senolytics to promote apoptosis of senescent cells, which is an innovation for cancer therapy. Here, our research found that wogonin, a well\u2010known natural flavonoid compound, not only had a potential to inhibit cell growth and proliferation but also induced cellular senescence in T\u2010cell malignancies with nonlethal concentration. Transcription activity of senescence\u2010suppression human telomerase reverse transcriptase (<jats:italic>hTERT<\/jats:italic>) and oncogenic <jats:italic>C-MYC<\/jats:italic> was suppressed in wogonin\u2010induced senescent cells, resulting in the inhibition of telomerase activity. We also substantiated the occurrence of DNA damage during the wogonin\u2010induced aging process. Results showed that wogonin increased the activity of senescence\u2010associated <jats:italic>\u03b2<\/jats:italic>\u2010galactosidase (SA\u2010<jats:italic>\u03b2<\/jats:italic>\u2010Gal) and activated the DNA damage response pathway mediated by p53. In addition, we found the upregulated expression of BCL\u20102 in senescent T\u2010cell malignancies because of the antiapoptotic properties of senescent cells. Following up this result, we identified a BCL\u20102 inhibitor Navitoclax (ABT\u2010263), which was highly effective in decreasing cell viability and inducing apoptotic cell death in wogonin\u2010induced senescent cells. Thus, the \u201cone\u2010two punch\u201d approach increased the sensibility of T\u2010cell malignancies with low expression of BCL\u20102 to Navitoclax. In conclusion, our research revealed that wogonin possesses potential antitumor effects based on senescence induction, offering a better insight into the development of novel therapeutic methods for T\u2010cell malignancies.<\/jats:p>","DOI":"10.1155\/2021\/5529518","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T23:50:53Z","timestamp":1632354653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["One\u2010Two Punch Therapy for the Treatment of T\u2010Cell Malignancies Involving p53\u2010Dependent Cellular 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