{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T07:15:19Z","timestamp":1775459719187,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":94,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Prostate Cancer"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prostate cancer is the second most commonly diagnosed cancer worldwide. Although androgen deprivation therapy initially demonstrates clinical benefit, disease relapse with more aggressive phenotypes frequently occurs. The acidic tumor microenvironment in solid tumors may alter drug responsiveness. This study investigates how extracellular pH influences the cytotoxic effects of bicalutamide in human prostate cancer cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PC3 and LNCaP cells were exposed to bicalutamide at varying concentrations at pH 7.4 and pH 6.8. IC50 values were determined using the MTT assay. Cell migration, apoptosis, and cell cycle distribution were evaluated by wound\u2010healing assay, annexin V\/PI staining, and DNA content analysis, respectively. The expression of\n                      <jats:italic>BAX<\/jats:italic>\n                      ,\n                      <jats:italic>BCL2<\/jats:italic>\n                      ,\n                      <jats:italic>E-cadherin<\/jats:italic>\n                      ,\n                      <jats:italic>N-cadherin<\/jats:italic>\n                      ,\n                      <jats:italic>SNAI1<\/jats:italic>\n                      ,\n                      <jats:italic>AR<\/jats:italic>\n                      , and\n                      <jats:italic>VEGF-C<\/jats:italic>\n                      was quantified by qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bicalutamide (140\u2009\u03bcg\/mL) reduced PC3 cell viability to 39.62% at pH 7.4 compared with 51.36% at pH 6.8. In LNCaP cells, viability declined to 33.64% at pH 7.4% and 56.09% at pH 6.8. Treated PC3 cells exhibited significantly greater migration at pH 6.8 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01). Early apoptosis in treated LNCaP cells was significantly reduced at pH 6.8 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Both cell lines demonstrated enhanced S phase accumulation and reduced G1\u2010phase distribution at pH 6.8. The\n                      <jats:italic>BAX<\/jats:italic>\n                      \/\n                      <jats:italic>BCL2<\/jats:italic>\n                      ratio was significantly decreased at pH 6.8, indicating the suppression of proapoptotic signaling. Additionally, genes associated with epithelial\u2013mesenchymal transition (EMT) were upregulated, and\n                      <jats:italic>VEGF-C<\/jats:italic>\n                      and\n                      <jats:italic>AR<\/jats:italic>\n                      expression increased at pH 6.8 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The efficacy of bicalutamide in prostate cancer cells is significantly influenced by extracellular pH. The drug exerts stronger cytotoxic, antimigratory, and proapoptotic effects at physiological pH (7.4) compared with acidic conditions (6.8).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/proc\/4321914","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T06:28:02Z","timestamp":1775456882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Tumor Microenvironmental Acidity on Bicalutamide Sensitivity in Prostate Cancer Cells"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4019-7714","authenticated-orcid":false,"given":"Pedram","family":"Golmohammadi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idris","family":"Haghani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-1512","authenticated-orcid":false,"given":"Iman","family":"Menbari Oskouie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1788-5282","authenticated-orcid":false,"given":"Rahil","family":"Mashhadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmadreza","family":"Rezaeian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-0362","authenticated-orcid":false,"given":"Seyed Mohammad Kazem","family":"Aghamir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-025-03573-z"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(08)60729-1"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05084-1"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52032-y"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0147-0272(03)00032-1"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/ppo.0b013e318161d13e"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.206"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mou.0000193384.39351.64"},{"key":"e_1_2_9_10_2","first-page":"481","article-title":"The Androgen Receptor as Putative Therapeutic Target in hormone-refractory Prostate Cancer","volume":"1","author":"Kageyama Y.","year":"2010","journal-title":"Frontiers in Anti-Cancer Drug Discovery"},{"key":"e_1_2_9_11_2","first-page":"239","article-title":"Androgen-Independent Prostate Cancer","author":"Schrijvers D.","year":"2007","journal-title":"Prostate Cancer."},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.04.008"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690416"},{"key":"e_1_2_9_14_2","first-page":"143","article-title":"Oxygen Supply to Malignant Tumors","author":"Vaupel P.","year":"2020","journal-title":"Tumor Blood Circulation"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.4.266"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34404"},{"key":"e_1_2_9_17_2","article-title":"Organellar Ph as an Emerging Vulnerability to Exploit in Cancer","author":"Galapate C. 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