{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:53:48Z","timestamp":1788587628148,"version":"build-2803163510"},"reference-count":74,"publisher":"SAGE Publications","issue":"17","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol).\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    Intravenous administration of Pter decreased human melanoma growth\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . However, Pter, at levels measured within the tumors, did not affect melanoma growth\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . Pter inhibited pituitary production of the adrenocorticotropin hormone (ACTH), decreased plasma levels of corticosterone, and thereby downregulated the glucocorticoid receptor- and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent antioxidant defense system in growing melanomas. Exogenous corticosterone or genetically induced Nrf2 overexpression in melanoma cells prevented the inhibition of tumor growth and decreased antioxidant defenses in these malignant cells. These effects and mechanisms were also found in mice bearing different human pancreatic cancers. Glutathione depletion (selected as an antimelanoma strategy) facilitated the complete elimination by chemotherapy of melanoma cells isolated from mice treated with Pter.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    Although bioavailability-related limitations may preclude direct anticancer effects\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , natural polyphenols may also interfere with the growth and defense of cancer cells by downregulating the pituitary gland-dependent ACTH synthesis.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic>\n                    <\/jats:bold>\n                    Pter downregulates glucocorticoid production, thus decreasing the glucocorticoid receptor and Nrf2-dependent signaling\/transcription and the antioxidant protection of melanoma and pancreatic cancer cells.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                    . 24, 974\u2013990.\n                  <\/jats:p>","DOI":"10.1089\/ars.2015.6437","type":"journal-article","created":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T21:41:52Z","timestamp":1449697312000},"page":"974-990","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":65,"title":["Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells\n                    <i>In Vivo<\/i>\n                    : A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism"],"prefix":"10.1177","volume":"24","author":[{"given":"Mar\u00eda","family":"Benlloch","sequence":"first","affiliation":[{"name":"San Vicente Martir Catholic University","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Obrador","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya L.","family":"Valles","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda L.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Antoni","family":"Sirerol","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Alc\u00e1cer","sequence":"additional","affiliation":[{"name":"Quir\u00f3n Hospital","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Pellicer","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Salvador","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concha","family":"Cerd\u00e1","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo T.","family":"S\u00e1ez","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]},{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Estrela","sequence":"additional","affiliation":[{"name":"University of Valencia","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,6,10]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.024"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"e_1_3_3_4_2","first-page":"221","article-title":"Cellular hydroperoxide metabolism: the roles of glutathione peroxidases and of catalase in liver","volume":"17","author":"Akerboom TP","year":"1981","unstructured":"Akerboom TP, , Gartner M, , and Sies H. Cellular hydroperoxide metabolism: the roles of glutathione peroxidases and of catalase in liver. Bull Eur Physiopathol Respir, 17 Suppl: 221\u2013227, 1981.","journal-title":"Bull Eur Physiopathol Respir"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00911-5"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408363.2011.631268"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1994.1126"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201400244"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-009-9154-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507471200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.373118"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.43.3.506"},{"key":"e_1_3_3_13_2","first-page":"229","article-title":"[Effect of hesperidin on behavior and HPA axis of rat model of chronic stress-induced depression]","volume":"38","author":"Cai L","year":"2013","unstructured":"Cai L, , Li R, , Wu QQ, , and Wu TN. [Effect of hesperidin on behavior and HPA axis of rat model of chronic stress-induced depression]. Zhongguo Zhong Yao Za Zhi, 38: 229\u2013233, 2013.","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3985"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0111814"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e3181c15963"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-011-9377-8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.12.005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2860257"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0195-84"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/10408360500523878"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3109\/08923977809027327"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605934200"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1593\/neo.04337"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05015-1"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05013-8"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2004.06.006"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/nure.12051"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4002"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402238"},{"key":"e_1_3_3_31_2","article-title":"NOV-002, a glutathione disulfide mimetic, suppresses tumor cell invasion and metastasis","author":"Gumireddy K","year":"2013","unstructured":"Gumireddy K, , Li A, , Cao L, , Yan J, , Liu L, , Xu X, , Pazoles C, , and Huang Q. NOV-002, a glutathione disulfide mimetic, suppresses tumor cell invasion and metastasis. J Carcinog Mutagen, 2013: pii-S7-002, 2013.","journal-title":"J Carcinog Mutagen"},{"key":"e_1_3_3_32_2","first-page":"512","article-title":"Isolation and characterization of dexamethasone-resistant mutants from human lymphoid cell line CEM-C7","volume":"1","author":"Harmon JM","year":"1981","unstructured":"Harmon JM, and Thompson EB. Isolation and characterization of dexamethasone-resistant mutants from human lymphoid cell line CEM-C7. Mol Cell Biol, 1: 512\u2013521, 1981.","journal-title":"Mol Cell Biol"},{"key":"e_1_3_3_33_2","first-page":"57","article-title":"Technique for performance and evaluation of parapharyngeal hypophysectomy in mice","volume":"45","author":"Hoff JB","year":"2006","unstructured":"Hoff JB, , Dysko R, , Kurachi S, , and Kurachi K. Technique for performance and evaluation of parapharyngeal hypophysectomy in mice. J Am Assoc Lab Anim Sci, 45: 57\u201362, 2006.","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2822"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/35030140"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-3025"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2009.01.008"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.208173"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-012-9623-7"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/80.1.15"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812062106"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057542"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf062816a"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2534"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2642"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-8"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044524"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0821-8"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2420631"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.196261"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30277"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096466"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3011285"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104459"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005870"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.06.015"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0363"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00324.2003"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201000044"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(04)01597-9"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0135"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-012-1448-y"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1892"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.06.006"},{"key":"e_1_3_3_65_2","first-page":"794","article-title":"Production of large amounts of hydrogen peroxide by human tumor cells","volume":"51","author":"Szatrowski TP","year":"1991","unstructured":"Szatrowski TP, and Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res, 51: 794\u2013798, 1991.","journal-title":"Cancer Res"},{"issue":"3","key":"e_1_3_3_66_2","article-title":"Fractionation of T and B cells using magnetic beads","volume":"3","author":"Thornton AM","year":"2003","unstructured":"Thornton AM. Fractionation of T and B cells using magnetic beads. Curr Protoc Immunol Chapter 3: Unit 3 5A, 2003.","journal-title":"Curr Protoc Immunol"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.009"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-72"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1469"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2010.08.039"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.10.022"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.10.484"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00920.x"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.09.009"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.425504"}],"container-title":["Antioxidants &amp; Redox Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2015.6437","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/ars.2015.6437","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/ars.2015.6437","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:56:14Z","timestamp":1779429374000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/ars.2015.6437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":74,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1089\/ars.2015.6437"],"URL":"https:\/\/doi.org\/10.1089\/ars.2015.6437","relation":{},"ISSN":["1523-0864","1557-7716"],"issn-type":[{"value":"1523-0864","type":"print"},{"value":"1557-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]}}}