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AuthorAkhtar, Sabah
AuthorZarif, Lubna
AuthorKuttikrishnan, Shilpa
AuthorPrabhu, Kirti S.
AuthorPatil, Kalyani
AuthorNisar, Sabah
AuthorAbou-Saleh, Haissam
AuthorMerhi, Maysaloun
AuthorDermime, Said
AuthorBhat, Ajaz A.
AuthorUddin, Shahab
Available date2023-07-06T11:28:26Z
Publication Date2022-11-16
Publication NameCancers
Identifierhttp://dx.doi.org/10.3390/cancers14225621
CitationAkhtar, S., Zarif, L., Kuttikrishnan, S., Prabhu, K. S., Patil, K., Nisar, S., ... & Uddin, S. (2022). 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. Cancers, 14(22), 5621.
ISSN2072-6694
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85142544543&origin=inward
URIhttp://hdl.handle.net/10576/45130
AbstractMultiple 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.
SponsorMedical Research Center, Grant no MRC-01-18-120 (SU) and MRC-01-20-858 (KSP), Hamad Medical Corporation, Doha, Qatar. The Open Access funding is provided by Qatar National Library.
Languageen
PublisherMultidisciplinary Digital Publishing Institute (MDPI)
Subjectanti-apoptotic proteins
apoptosis
guggulsterone
HMGB1
JAK/STAT signaling
multiple myeloma
TitleGuggulsterone Induces Apoptosis in Multiple Myeloma Cells by Targeting High Mobility Group Box 1 via Janus Activated Kinase/Signal Transducer and Activator of Transcription Pathway
TypeArticle
Issue Number22
Volume Number14
dc.accessType Open Access


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