Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines

Jorge, Joana; Petronilho, Sara; Alves, Raquel; Coucelo, Margarida; Gonçalves, Ana Cristina; Costa, Nascimento; Sarmento‐Ribeiro, Ana Bela

doi:10.1007/s10637-019-00796-2

Cited by 19 publications

(15 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When SF3B1 was inhibited, the cell cycle in the AGS and MKN28 cells was arrested, and apoptosis increased. This finding was consistent with the results of previous studies on human malignant cell lines [19].…”

Section: Discussionsupporting

confidence: 94%

Inhibition of Splicing Factor 3b Subunit 1 (SF3B1) Reduced Cell Proliferation, Induced Apoptosis and Resulted in Cell Cycle Arrest by Regulating Homeobox A10 (HOXA10) Splicing in AGS and MKN28 Human Gastric Cancer Cells

et al. 2020

View full text Add to dashboard Cite

Background: Small nuclear ribonucleoproteins (snRNPs) complexes of protein and noncoding RNA accumulate in the cell nucleus and catalyze pre-mRNA splicing to form the spliceosome. This study aimed to investigate the role of the spliceosome, splicing factor 3b subunit 1 (SF3B1), in AGS and MKN28 human gastric cancer cells in vitro, including gene knockdown with small interfering RNA (siRNA), and the use of the selective mRNA splicing inhibitor of SF3B1, pladienolide B. Material/Methods: In AGS and MKN28 human gastric cancer cells, SF3B1expression was inhibited with siRNA and pladienolide B. Following SF3B1 inhibition, the Cell Counting Kit-8 (CCK-8) assay measured cell proliferation, and flow cytometry was used to investigate cell apoptosis and cell cycle arrest. The downstream HOXA10 and AKT pathways were studied by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. The presence of alternative splicing, or differential splicing, of single-gene coding for multiple proteins, was analyzed using The Cancer Genome Atlas (TCGA) SpliceSeq. Results: Inhibition of SF3B1 reduced the proliferation rate of AGS and MKN28 human gastric cancer cells by inducing apoptosis and G2/M phase arrest. SF3B1 knockdown resulted in reduced homeobox A10 (HOXA10) mRNA expression and expression of long noncoding RNA (lncRNA) isoforms of HOXA10 (exons 1 and 3) and HOXA10 (exons 2 and 3). SF3B1 inhibition increased PTEN levels and reduced AKT protein phosphorylation. Conclusions: In AGS and MKN28 human gastric cancer cells in vitro, inhibition of SF3B1 reduced cell proliferation, induced apoptosis, and resulted in cell cycle arrest by regulating HOXA10 splicing.

show abstract

Section: Discussionsupporting

confidence: 94%

Inhibition of Splicing Factor 3b Subunit 1 (SF3B1) Reduced Cell Proliferation, Induced Apoptosis and Resulted in Cell Cycle Arrest by Regulating Homeobox A10 (HOXA10) Splicing in AGS and MKN28 Human Gastric Cancer Cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It is interesting that although Plad B and 3p-hpRNA synergized for IFN-I response in A549 cells, they did not synergize for cytotoxicity. Plad B has been characterized to induce both cell-cycle arrest and apoptosis ( 19 , 45 , 46 , 50 ). RIG-I agonists such as 3p-hpRNA have been characterized to induce apoptosis and pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

Modulation of SF3B1 in the pre-mRNA spliceosome induces a RIG-I-dependent type I IFN response

Chang

Zhou

Iyengar

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

“…Indeed, splicing isoforms have been reported for key cell-cycle factors including cell division cycle 25 (CDC25), aurora kinase B (AURKB), CDC-Like kinase 1 (CLK1) and CDK2. 37 , 38 Thus, tumor cell proliferation rate might be responsible for high SF3B1 levels observed in these cells, but more investigations are needed. Despite the low mutational burden reported for splicing factors in MM, a striking anti-tumor effects of splicing modulators was observed to be associated with a significant change in MCL1 spliced isoforms in treated cells than specific control.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis reprogramming triggered by splicing inhibitors sensitizes multiple myeloma cells to Venetoclax treatment

et al. 2021

View full text Add to dashboard Cite

Identification of novel vulnerabilities in the context of therapeutic resistance is emerging as key challenge for cancer treatment. Recent studies have detected pervasive aberrant splicing in cancer cells, supporting its targeting for novel therapeutic strategies. Here, we evaluated the expression of several spliceosome machinery components in multiple myeloma (MM) cells and the impact of splicing modulation on tumor cell growth and viability. A comprehensive gene expression analysis confirmed the reported deregulation of spliceosome machinery components in MM cells, compared to normal plasma cells (PCs) from healthy donors, with its pharmacological and genetic modulation resulting in impaired growth and survival of MM cell lines and patient-derived malignant PCs. Consistent with this, transcriptomic analysis revealed deregulation of BCL2 family members, including decrease of antiapoptotic long form of myeloid cell leukemia-1 (MCL1) expression, as crucial for “priming” MM cells for Venetoclax activity in vitro and in vivo, irrespective of t(11;14) status. Overall, our data provide a rationale for supporting the clinical use of splicing modulators as a strategy to reprogram apoptotic dependencies and make all MM patients more vulnerable to BCL2 inhibitors.

show abstract

Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines

Cited by 19 publications

References 33 publications

Inhibition of Splicing Factor 3b Subunit 1 (SF3B1) Reduced Cell Proliferation, Induced Apoptosis and Resulted in Cell Cycle Arrest by Regulating Homeobox A10 (HOXA10) Splicing in AGS and MKN28 Human Gastric Cancer Cells

Inhibition of Splicing Factor 3b Subunit 1 (SF3B1) Reduced Cell Proliferation, Induced Apoptosis and Resulted in Cell Cycle Arrest by Regulating Homeobox A10 (HOXA10) Splicing in AGS and MKN28 Human Gastric Cancer Cells

Modulation of SF3B1 in the pre-mRNA spliceosome induces a RIG-I-dependent type I IFN response

Apoptosis reprogramming triggered by splicing inhibitors sensitizes multiple myeloma cells to Venetoclax treatment

Contact Info

Product

Resources

About