{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:08:42Z","timestamp":1788484122716,"version":"build-2803163510"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"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:p>Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains clinically challenging due to tumor heterogeneity and resistance to standard microtubule-targeting agents, such as docetaxel and cabazitaxel. The natural pterocarpan (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-PTC] has previously shown selective cytotoxicity and disruption of bipolar spindle assembly in mCRPC PC-3 cells yet its full mechanism of action and global proteomic impact remain uncharacterized. PC-3 cells were treated with (+)-PTC (2.0\u00a0\u00b5M or 8.0\u00a0\u00b5M) for 24\u00a0h and assessed by flow cytometry (Annexin V and rhodamine 123) Western blot, and caspase-3\/7 luminescence assays. Global proteomic profiling was performed by quantitative LC-MS\/MS using a 2D nano-UPLC data-independent acquisition platform with nocodazole (0.25\u00a0\u00b5M, microtubule depolymerizer) and monastrol (50\u00a0\u00b5M, Eg5 inhibitor) as comparators. (+)-PTC-induced concentration-dependent apoptosis (19.8% early apoptotic cells at 2.0\u00a0\u00b5M; 26.1% at 8.0\u00a0\u00b5M) and progressive mitochondrial membrane depolarization. Western blot and caspase activities assays confirmed upregulation of BAX and caspase-7, consistent with intrinsic pathway activation. Proteomic analysis identified 212 differentially expressed proteins (DEPs) in (+)-PTC-treated cells, with over 80% overlap with nocodazole-treated cells (82% among upregulated and 84% among downregulated proteins), while clustering with monastrol was markedly lower. The top upregulated proteins, TTLL3, ANAPC7, PIK3CA, ARID4B, and COL16A1, are linked to microtubule dynamics and cell cycle regulation; the main downregulated, namely KDM2B, PTOV1, YWHAQ, PSMB6, and PRKCB, are involved in cell survival, protein homeostasis and mitotic checkpoint control. These findings provide proteomic evidence that (+)-PTC interferes with cytoskeletal protein dynamics and promotes apoptosis in mCRPC and so warranting its further investigation as a candidate anti-cancer scaffold.<\/jats:p>","DOI":"10.3389\/fphar.2026.1770249","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:06:00Z","timestamp":1780466760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The pterocarpan (+)-PTC modulates cytoskeletal proteins and induces apoptosis in metastatic castration-resistant prostate cancer: a proteomic perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Jos\u00e9","family":"de Brito Vieira Neto","sequence":"first","affiliation":[{"name":"Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Cear\u00e1","place":["Fortaleza, 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