{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:03:33Z","timestamp":1789153413454,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA203108"],"award-info":[{"award-number":["R01 CA203108"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR063786"],"award-info":[{"award-number":["R01 AR063786"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer cachexia, characterized by muscle and fat tissue wasting, is a major determinant of cancer\u2010related mortality without established treatment. Recent animal data revealed that cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 as surface proteins on extracellular vesicles (EVs). Here, we test a therapeutic strategy for ameliorating cancer cachexia by inhibiting the release of Hsp70 and Hsp90 using proton pump inhibitor omeprazole.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Omeprazole effect on Hsp70\/90 release through EVs by Lewis lung carcinoma (LLC) cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      , serum levels of Hsp70\/90 and Hsp70\/90\u2010carrying EVs in LLC tumour\u2010bearing mice, and LLC\u2010induced muscle protein degradation pathways in C2C12 myotubes and mice were determined. Omeprazole effect on endolysosomal pH and Rab27b expression in LLC cells were analysed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Omeprazole treatment of LLC cells inhibited Hsp70\/90 and Hsp70\/90\u2010carrying EV release in a dose\u2010dependent manner (1 to 10\u00a0\u03bcM) and attenuated the catabolic activity of LLC cell\u2010conditioned medium on C2C12 myotubes. Systemic omeprazole administration to LLC tumour\u2010bearing mice (5\u00a0mg\/kg\/day subcutaneously) for 2\u00a0weeks blocked elevation of serum Hsp70, Hsp90, and Hsp70\/90\u2010carrying EVs, abrogated skeletal muscle catabolism, and prevented loss of muscle function as well as muscle and epididymal fat mass without altering tumour growth. Consequently, median survival increased by 23.3%. Mechanistically, omeprazole increased cancer cell endolysosomal pH level dose\u2010dependently (0.1 to 1\u00a0\u03bcM) by inhibiting vacuolar H\n                      <jats:sup>+<\/jats:sup>\n                      \u2010ATPase. Further, omeprazole suppressed the highly elevated expression of Rab27b, a key regulator of EV release, in LLC cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Omeprazole ameliorates cancer cachexia by inhibiting cancer cell release of Hsp70 and Hsp90.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12851","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T21:53:06Z","timestamp":1635889986000},"page":"636-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Ameliorating cancer cachexia by inhibiting cancer cell release of Hsp70 and Hsp90 with omeprazole"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhelong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"},{"name":"Biochemistry and Cell Biology Program MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael X.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"},{"name":"Biochemistry and Cell Biology Program MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"},{"name":"Biochemistry and Cell Biology Program MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences  Houston TX USA"},{"name":"The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases University of Texas Health Science Center  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"},{"name":"The Vivian L. Smith Department of Neurosurgery The University of Texas Health Science Center at Houston  Houston TX USA"},{"name":"Department of Medicine The University of Oklahoma Health Sciences Center  Oklahoma City OK USA"},{"name":"Department of Surgery The University of Oklahoma Health Sciences Center  Oklahoma City OK USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0811-2790","authenticated-orcid":false,"given":"Yi\u2010Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at Houston  Houston TX USA"},{"name":"Biochemistry and Cell Biology Program MD Anderson Cancer Center 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