Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway
<p dir="ltr">Multiple 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 therape...
محفوظ في:
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| مؤلفون آخرون: | , , , , , , , , , |
| منشور في: |
2023
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| _version_ | 1864513530442547200 |
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| author | Shilpa Kuttikrishnan (3520079) |
| author2 | Fareed Ahmad (134672) Jericha M. Mateo (17563293) Kirti S. Prabhu (4246144) Tamam El‐Elimat (17714580) Nicholas H. Oberlies (326437) Cedric J. Pearce (1364220) Ammira S. Alshabeeb Akil (15430143) Ajaz A. Bhat (12984701) Feras Q. Alali (2691907) Shahab Uddin (154400) |
| author2_role | author author author author author author author author author author |
| author_facet | Shilpa Kuttikrishnan (3520079) Fareed Ahmad (134672) Jericha M. Mateo (17563293) Kirti S. Prabhu (4246144) Tamam El‐Elimat (17714580) Nicholas H. Oberlies (326437) Cedric J. Pearce (1364220) Ammira S. Alshabeeb Akil (15430143) Ajaz A. Bhat (12984701) Feras Q. Alali (2691907) Shahab Uddin (154400) |
| author_role | author |
| dc.creator.none.fl_str_mv | Shilpa Kuttikrishnan (3520079) Fareed Ahmad (134672) Jericha M. Mateo (17563293) Kirti S. Prabhu (4246144) Tamam El‐Elimat (17714580) Nicholas H. Oberlies (326437) Cedric J. Pearce (1364220) Ammira S. Alshabeeb Akil (15430143) Ajaz A. Bhat (12984701) Feras Q. Alali (2691907) Shahab Uddin (154400) |
| dc.date.none.fl_str_mv | 2023-10-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1002/cbin.12101 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Neosetophomone_B_induces_apoptosis_in_multiple_myeloma_cells_via_targeting_of_AKT_SKP2_signaling_pathway/24954642 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences AKT caspases drug synergy multiple myeloma neosetophomone B SKP2 |
| dc.title.none.fl_str_mv | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Multiple 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Biology International<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/cbin.12101" target="_blank">https://dx.doi.org/10.1002/cbin.12101</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_244e06a3296d80415129d065eea4c236 |
| identifier_str_mv | 10.1002/cbin.12101 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24954642 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathwayShilpa Kuttikrishnan (3520079)Fareed Ahmad (134672)Jericha M. Mateo (17563293)Kirti S. Prabhu (4246144)Tamam El‐Elimat (17714580)Nicholas H. Oberlies (326437)Cedric J. Pearce (1364220)Ammira S. Alshabeeb Akil (15430143)Ajaz A. Bhat (12984701)Feras Q. Alali (2691907)Shahab Uddin (154400)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesCardiovascular medicine and haematologyOncology and carcinogenesisPharmacology and pharmaceutical sciencesAKTcaspasesdrug synergymultiple myelomaneosetophomone BSKP2<p dir="ltr">Multiple 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Biology International<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/cbin.12101" target="_blank">https://dx.doi.org/10.1002/cbin.12101</a></p>2023-10-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/cbin.12101https://figshare.com/articles/journal_contribution/Neosetophomone_B_induces_apoptosis_in_multiple_myeloma_cells_via_targeting_of_AKT_SKP2_signaling_pathway/24954642CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/249546422023-10-01T00:00:00Z |
| spellingShingle | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway Shilpa Kuttikrishnan (3520079) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences AKT caspases drug synergy multiple myeloma neosetophomone B SKP2 |
| status_str | publishedVersion |
| title | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway |
| title_full | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway |
| title_fullStr | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway |
| title_full_unstemmed | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway |
| title_short | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway |
| title_sort | Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT/SKP2 signaling pathway |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Cardiovascular medicine and haematology Oncology and carcinogenesis Pharmacology and pharmaceutical sciences AKT caspases drug synergy multiple myeloma neosetophomone B SKP2 |