{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:08:16Z","timestamp":1788872896046,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"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":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Androgen receptor (AR) plays a pivotal role in the development and progression of prostate cancer by regulating the expression of androgen\u2010responsive genes. AR must translocate into the nucleus to exert its gene\u2010regulatory functions. Disruption in AR nuclear localization or its cytoplasmic retention hampers its ability to activate target genes, thus impeding prostate cancer progression.\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Taraxacum officinale<\/jats:italic>\n                    <\/jats:styled-content>\n                    (dandelion) is a medicinal herb with potent anticancer properties, rich in antioxidants, flavonoids, and nutrients, dandelion serves as a promising herbal nutraceutical and superfood for cancer prevention. The study aimed to explore plant\u2010based molecules from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Taraxacum officinale<\/jats:italic>\n                    <\/jats:styled-content>\n                    (dandelion) capable of modulating AR nuclear localization in recurrent prostate cancer cells in\u00a0vitro and in\u00a0vivo. 400 plants were collected and 25,000 extracts were prepared using solvents of varying polarity (Indian Patent Grant No. 499495) and were screened for abrogation of Nuclear\u2010cytoplasmic localization of AR. Phytochemical screening led to the isolation of Phytol (3,7,11,15\u2010tetramethylhexadec\u20102\u2010en\u20101\u2010ol) (TaxO) from the hexane extract of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Taraxacum officinale<\/jats:italic>\n                    <\/jats:styled-content>\n                    L leaves. The effects of TaxO was evaluated in\u00a0vitro using the castration\u2010resistant prostate cancer cell line C4\u20102, androgen\u2010responsive cell line LNCaP, and AR\u2010negative cell line PC3. Expression of AR and androgen\u2010responsive genes, including EAF2, PSA, and CALR, were\u00a0analyzed via RT\u2010PCR. Inhibition of cellular proliferation and migration was assessed in\u00a0vitro. Comparative transcriptomic analysis (RNA\u2010Seq) was conducted to elucidate the mechanistic differences between treated and control groups. Molecular docking studies were conducted to evaluate interactions between TaxO and the AR ligand\u2010binding domain. Finally, in\u00a0vivo efficacy was examined using C4\u20102, LNCaP and PC3 xenograft mouse models, including immunohistochemistry (IHC) for AR, Ki67, CD31, and PSA. PK\/PD analysis was carried out to assess the safety profile of TaxO. TaxO abrogated nuclear localization of GFP\u2010tagged AR. TaxO significantly downregulated AR\u2010responsive gene expression, EAF2, ELL2, PSA, and CALR and inhibited cell proliferation and migration of C4\u20102 and LNCaP cells. Transcriptomic profiling revealed major alterations in oncogenic signaling pathways post\u2010TaxO treatment. Molecular docking confirmed strong binding between TaxO and the AR ligand\u2010binding domain, driven by van der Waals forces and hydrogen bonding. In the xenograft model, TaxO markedly reduced tumor volume and doubled the life expectancy of mice harboring C4\u20102 and LNCaP prostate cancer cells. IHC revealed downregulation of AR and PSA levels and showed a reduction in Ki67 and CD31 index. However, PC3 cells were not affected by TaxO implicating that TaxO inhibits cancer cell growth through the AR\u2010mediated pathway. The study demonstrates that TaxO, a phytochemical (Phytol) isolated from the hexane extract of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Taraxacum officinale<\/jats:italic>\n                    <\/jats:styled-content>\n                    leaves, effectively modulates androgen receptor (AR) nuclear localization, thereby inhibiting prostate cancer progression. In\u00a0vitro, TaxO significantly downregulated AR and androgen\u2010responsive gene expression (EAF2, ELL2, PSA, CALR), reduced cell proliferation and migration in AR\u2010positive C4\u20102 and LNCaP cell lines but showed no effect on AR\u2010negative PC3 cells, indicating an AR\u2010mediated mechanism. Transcriptomic analysis revealed disruptions in oncogenic signaling pathways, while molecular docking confirmed TaxO's strong binding to the AR ligand\u2010binding domain. In\u00a0vivo, TaxO reduced tumor volume, downregulated AR, PSA, Ki67, and CD31 protein expression, and doubled life expectancy in C4\u20102 and LNCaP xenograft mouse models. Pharmacokinetic and pharmacodynamic analyses further supported TaxO's favorable safety profile. These findings highlight TaxO as a promising plant\u2010based therapeutic candidate for targeting AR\u2010driven prostate cancer, warranting further clinical investigation.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70115","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T07:38:22Z","timestamp":1770622702000},"page":"2171-2196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phytol Suppresses Androgen Receptor Nuclear Localization and Doubles Survival in Nude Mice Bearing Castration\u2010Resistant Prostate Cancer Xenografts"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1668-3259","authenticated-orcid":false,"given":"Wasia","family":"Showket","sequence":"first","affiliation":[{"name":"Transcriptomics Laboratory (K\u2010Lab), Division of Plant Biotechnology Sher\u2010e\u2010Kashmir University of Agricultural Sciences and Technology of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2306-9237","authenticated-orcid":false,"given":"Dar","family":"Murtaza","sequence":"additional","affiliation":[{"name":"Transcriptomics Laboratory (K\u2010Lab), Division of Plant Biotechnology Sher\u2010e\u2010Kashmir University of Agricultural Sciences and Technology of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasmeen J.","family":"Parihar","sequence":"additional","affiliation":[{"name":"Transcriptomics Laboratory (K\u2010Lab), Division of Plant Biotechnology Sher\u2010e\u2010Kashmir University of Agricultural Sciences and Technology of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5851-3832","authenticated-orcid":false,"given":"Suhail","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Plant Biotechnology, Centre for Plant Molecular Biology and Biotechnology Tamil Nadu Agricultural University  Coimbatore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahoor A.","family":"Dar","sequence":"additional","affiliation":[{"name":"Transcriptomics Laboratory (K\u2010Lab), Division of Plant Biotechnology Sher\u2010e\u2010Kashmir University of Agricultural Sciences and Technology of Kashmir  Srinagar Jammu and Kashmir India"},{"name":"Department of Biotechnology University of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Inam\u2010ul\u2010Haq","sequence":"additional","affiliation":[{"name":"Transcriptomics Laboratory (K\u2010Lab), Division of Plant Biotechnology Sher\u2010e\u2010Kashmir University of Agricultural Sciences and Technology of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imtiyaz A.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Skims Soura  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Afsahul","family":"Kalam","sequence":"additional","affiliation":[{"name":"Department of IImulAdvia (Pharmacology), RRIUM University of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Mukhtar","sequence":"additional","affiliation":[{"name":"Division of Food Science and Technology Sher\u2010e\u2010Kashmir University of Agricultural Sciences and Technology of Kashmir  Srinagar Jammu and Kashmir India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javeed A.","family":"Mugloo","sequence":"additional","affiliation":[{"name":"Division of Silviculture, Agriforestry Sher\u2010e\u2010Kashmir University of Agricultural Sciences and Technology of Kashmir  Ganderbal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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