Bavachin induces the apoptosis of multiple myeloma cell lines by inhibiting the activation of nuclear factor kappa B and signal transducer and activator of transcription 3

Abstract Background Constitutively activated STAT3 (Signal transducer and activator of transcription 3) has been seen in Multiple Myeloma (MM). However, STAT3 regulator in MM remains enigmatic. Methods Herein, we applied public dataset analysis and identified USP25 (Ubiquitin carboxyl-terminal hydrolase 25) was a potential regulator of STAT3. We further applied western blot and IP to confirm the relation between USP25 and STAT3. Furthermore, we used cell cycle assay to assess the effect USP25 on MM cell cycle.RestultsUSP25 highly expressed in MM CD138+ cells, and support MM cell proliferation. In protein level, USP25 take part in IL-6/USP25/STAT3 axis and could directly down-regulated STAT3 ubiquitination. Using truncated form of USP25, we also proved UCH (Ubiquitin carboxyl-terminal hydrolase) domain of USP25 is critical for USP25-STAT3 binding, UIM (Ubiquitin interacting motif) domain is required for STAT3 ubiquitination, we further proved cell cycle changed by USP25 required STAT3 and cyclinD1, suggesting USP25 inhibition is promising in STAT3, cyclinD1 abnormal MM patients.

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Bone sialoprotein mRNA and protein expression in human multiple myeloma cell lines and patients

British Journal of Haematology ◽

10.1046/j.1365-2141.2000.02506.x ◽

2000 ◽

Vol 111 (4) ◽

pp. 1118-1121 ◽

Cited By ~ 5

Author(s):

A. Bellahcene ◽

I. Van Riet ◽

C. de Greef ◽

N. Antoine ◽

M. F. Young ◽

...

Keyword(s):

Multiple Myeloma ◽

Protein Expression ◽

Cell Lines ◽

Myeloma Cell ◽

Bone Sialoprotein ◽

Multiple Myeloma Cell ◽

Human Multiple Myeloma ◽

Mrna And Protein Expression

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The role of nuclear factor-[kappa ]B in the biology and treatment of multiple myeloma

Seminars in Oncology ◽

10.1053/sonc.2001.29542 ◽

2001 ◽

Vol 28 (6) ◽

pp. 626-633 ◽

Cited By ~ 3

Author(s):

James R. Berenson ◽

Hongjin M. Ma ◽

Robert Vescio

Keyword(s):

Multiple Myeloma ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Nuclear Factor Kappa

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HDAC6-Selective Inhibitor Overcomes Bortezomib Resistance in Multiple Myeloma

International Journal of Molecular Sciences ◽

10.3390/ijms22031341 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1341

Author(s):

Sang Wu Lee ◽

Soo-Keun Yeon ◽

Go Woon Kim ◽

Dong Hoon Lee ◽

Yu Hyun Jeon ◽

...

Keyword(s):

Multiple Myeloma ◽

Nuclear Factor Kappa B ◽

Selective Inhibitor ◽

Signal Transducer ◽

Histone Deacetylase 6 ◽

Cell Growth Inhibition ◽

Cancer Cell Growth ◽

Extracellular Signal ◽

Hdac6 Inhibitor ◽

Transcription 3

Although multiple myeloma (MM) patients benefit from standard bortezomib (BTZ) chemotherapy, they develop drug resistance, resulting in relapse. We investigated whether histone deacetylase 6 (HDAC6) inhibitor A452 overcomes bortezomib resistance in MM. We show that HDAC6-selective inhibitor A452 significantly decreases the activation of BTZ-resistant markers, such as extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NF-κB), in acquired BTZ-resistant MM cells. Combination treatment of A452 and BTZ or carfilzomib (CFZ) synergistically reduces BTZ-resistant markers. Additionally, A452 synergizes with BTZ or CFZ to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3), resulting in decreased expressions of low-molecular-mass polypeptide 2 (LMP2) and LMP7. Furthermore, combining A452 with BTZ or CFZ leads to synergistic cancer cell growth inhibition, viability decreases, and apoptosis induction in the BTZ-resistant MM cells. Overall, the synergistic effect of A452 with CFZ is more potent than that of A452 with BTZ in BTZ-resistant U266 cells. Thus, our findings reveal the HDAC6-selective inhibitor as a promising therapy for BTZ-chemoresistant MM.

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The oral protein-kinase Cβinhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines

Leukemia & Lymphoma ◽

10.1080/10428190802078289 ◽

2008 ◽

Vol 49 (7) ◽

pp. 1374-1383 ◽

Cited By ~ 25

Author(s):

Antonino Neri ◽

Sandra Marmiroli ◽

Pierfrancesco Tassone ◽

Luigia Lombardi ◽

Lucia Nobili ◽

...

Keyword(s):

Multiple Myeloma ◽

Protein Kinase ◽

Cell Lines ◽

Myeloma Cell ◽

Akt Pathway ◽

Multiple Myeloma Cell

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Simvastatin Induces Death of Multiple Myeloma Cell Lines

Journal of Investigative Medicine ◽

10.1136/jim-52-05-34 ◽

2004 ◽

Vol 52 (5) ◽

pp. 335-344 ◽

Cited By ~ 11

Author(s):

Naomi Gronich ◽

Liat Drucker ◽

Hava Shapiro ◽

Judith Radnay ◽

Shai Yarkoni ◽

...

Keyword(s):

Cell Cycle ◽

Multiple Myeloma ◽

Cell Death ◽

Cell Lines ◽

Myeloma Cell ◽

Cytoplasmic Calcium ◽

Multiple Myeloma Cell ◽

Cycle Arrest ◽

Rpmi 8226

BackgroundAccumulating reports indicate that statins widely prescribed for hypercholesteromia have antineoplastic activity. We hypothesized that because statins inhibit farnesylation of Ras that is often mutated in multiple myeloma (MM), as well as the production of interleukin (IL)-6, a key cytokine in MM, they may have antiproliferative and/or proapoptotic effects in this malignancy.MethodsU266, RPMI 8226, and ARH77 were treated with simvastatin (0-30 μM) for 5 days. The following aspects were evaluated: viability (IC50), cell cycle, cell death, cytoplasmic calcium ion levels, supernatant IL-6 levels, and tyrosine kinase activity.ResultsExposure of all cell lines to simvastatin resulted in reduced viability with IC50s of 4.5 μM for ARH77, 8 μM for RPMI 8226, and 13 μM for U266. The decreased viability is attributed to cell-cycle arrest (U266, G1; RPMI 8226, G2M) and cell death. ARH77 underwent apoptosis, whereas U266 and RPMI 8226 displayed a more necrotic form of death. Cytoplasmic calcium levels decreased significantly in all treated cell lines. IL-6 secretion from U266 cells was abrogated on treatment with simvastatin, whereas total tyrosine phosphorylation was unaffected.ConclusionsSimvastatin displays significant antimyeloma activity in vitro. Further research is warranted for elucidation of the modulated molecular pathways and clinical relevance.

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