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AuthorKuttikrishnan, Shilpa
AuthorAhmad, Fareed
AuthorMateo, Jericha M.
AuthorPrabhu, Kirti S.
AuthorEl-Elimat, Tamam
AuthorOberlies, Nicholas H.
AuthorPearce, Cedric J.
AuthorAkil, Ammira S.Alshabeeb
AuthorBhat, Ajaz A.
AuthorAlali, Feras Q.
AuthorUddin, Shahab
Available date2024-01-30T11:03:06Z
Publication Date2023-10-26
Publication NameCell Biology International
Identifierhttp://dx.doi.org/10.1002/cbin.12101
CitationKuttikrishnan, S., Ahmad, F., Mateo, J. M., Prabhu, K. S., El‐Elimat, T., Oberlies, N. H., ... & Uddin, S. (2023). Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway. Cell Biology International.
ISSN1065-6995
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85175040049&origin=inward
URIhttp://hdl.handle.net/10576/51388
AbstractMultiple myeloma (MM) is a hematologic malignancy associated with malignant plasma cell proliferation in the bone marrow. Despite the available treatments, drug resistance and adverse side effects pose significant challenges, underscoring the need for alternative therapeutic strategies. Natural products, like the fungal metabolite neosetophomone B (NSP-B), have emerged as potential therapeutic agents due to their bioactive properties. Our study investigated NSP-B's antitumor effects on MM cell lines (U266 and RPMI8226) and the involved molecular mechanisms. NSP-B demonstrated significant growth inhibition and apoptotic induction, triggered by reduced AKT activation and downregulation of the inhibitors of apoptotic proteins and S-phase kinase protein. This was accompanied by an upregulation of p21Kip1 and p27Cip1 and an elevated Bax/BCL2 ratio, culminating in caspase-dependent apoptosis. Interestingly, NSP-B also enhanced the cytotoxicity of bortezomib (BTZ), an existing MM treatment. Overall, our findings demonstrated that NSP-B induces caspase-dependent apoptosis, increases cell damage, and suppresses MM cell proliferation while improving the cytotoxic impact of BTZ. These findings suggest that NSP-B can be used alone or in combination with other medicines to treat MM, highlighting its importance as a promising phytoconstituent in cancer therapy.
SponsorQatar National Library provided open access of this article. This work was supported by grants funded by the Medical Research Center (MRC), Hamad Medical Corporation, Doha, Qatar (MRC‐01‐21‐301).
Languageen
PublisherWiley-Blackwell
SubjectAKT
caspases
drug synergy
multiple myeloma
neosetophomone B
SKP2
TitleNeosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway
TypeArticle
Issue Number2
Volume Number48
ESSN1095-8355
dc.accessType Open Access


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