{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:59:36Z","timestamp":1788278376047,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Center","award":["MRC-01-18-120"],"award-info":[{"award-number":["MRC-01-18-120"]}]},{"name":"Medical Research Center","award":["MRC-01-20-858"],"award-info":[{"award-number":["MRC-01-20-858"]}]},{"name":"Qatar National Library","award":["MRC-01-18-120"],"award-info":[{"award-number":["MRC-01-18-120"]}]},{"name":"Qatar National Library","award":["MRC-01-20-858"],"award-info":[{"award-number":["MRC-01-20-858"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) is a hematological disorder characterized by the abnormal expansion of plasma cells in the bone marrow. Despite great advances over the past three decades in discovering the efficacious therapies for MM, the disease remains incurable for most patients owing to emergence of drug-resistant cancerous cells. Guggulsterone (GS), a phytosteroid, extracted from the gum resin of guggul plant, has displayed various anticancer activities in vitro and in vivo; however, the molecular mechanisms of its anticancer activity have not been evaluated in MM cells. Therefore, in this study, we investigated the anticancer activity of GS in various MM cell lines (U266, MM.1S, and RPMI 8226) and the mechanisms involved. GS treatment of MM cells caused inhibition of cell proliferation and induction of apoptotic cell death as indicated by increased Bax protein expression, activation of caspases, and cleavage of poly (ADP-ribose) polymerase. This was associated with the downregulation of various proliferative and antiapoptotic gene products, including cyclin D, Bcl-2, Bcl-xL, and X-linked inhibitor of apoptosis protein. GS also suppressed the constitutive and interleukin 6-induced activation of STAT3. Interestingly, the inhibition of Janus activated kinase or STAT3 activity by the specific inhibitors or by siRNA knockdown of STAT3 resulted in the downregulation of HMGB1, suggesting an association between GS, STAT3, and HMGB1. Finally, GS potentiated the anticancer effects of bortezomib (BTZ) in MM cells. Herein, we demonstrated that GS could be a potential therapeutic agent for the treatment of MM, possibly alone or in combination with BTZ.<\/jats:p>","DOI":"10.3390\/cancers14225621","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:27:44Z","timestamp":1668655664000},"page":"5621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Guggulsterone Induces Apoptosis in Multiple Myeloma Cells by Targeting High Mobility Group Box 1 via Janus Activated Kinase\/Signal Transducer and Activator of Transcription Pathway"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1481-6708","authenticated-orcid":false,"given":"Sabah","family":"Akhtar","sequence":"first","affiliation":[{"name":"Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubna","family":"Zarif","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Biological Science Program, Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Kuttikrishnan","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti S.","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyani","family":"Patil","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabah","family":"Nisar","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Sidra Medicine, Doha 26999, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3460-1413","authenticated-orcid":false,"given":"Haissam","family":"Abou-Saleh","sequence":"additional","affiliation":[{"name":"Biological Science Program, Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha 2713, Qatar"},{"name":"Biomedical Research Center, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8016-3699","authenticated-orcid":false,"given":"Maysaloun","family":"Merhi","sequence":"additional","affiliation":[{"name":"National Center for Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5526-7496","authenticated-orcid":false,"given":"Said","family":"Dermime","sequence":"additional","affiliation":[{"name":"National Center for Cancer Care and Research, Hamad Medical Corporation, Doha 3050, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3640-6275","authenticated-orcid":false,"given":"Ajaz A.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Sidra Medicine, Doha 26999, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1886-6710","authenticated-orcid":false,"given":"Shahab","family":"Uddin","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar"},{"name":"Laboratory of Animal Research Center, Qatar University, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1038\/s41467-021-22804-x","article-title":"Co-evolution of tumor and immune cells during progression of multiple myeloma","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. 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