Myofibrillogenesis regulator-1 promotes cell adhesion and migration in human hepatoma cells

Zhao, Wei; He, Hongwei; Ren, Kaihuan; Zhang, Hao; Chen, Yi; Shao, Rong‐Guang

doi:10.1007/s11434-013-5933-9

Cited by 6 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Hippo pathway plays an important role in cell proliferation, differentiation and DNA damage, and YAP is the major downstream effector of the Hippo pathway [ 31 – 33 ]. Some studies showed that YAP participated in DNA damage-induced apoptosis and is the key role in tumor suppression independent of p53, YAP knockdown sensitized tumor cells to chemotherapy and radiation effects via increased accumulation of DNA damage [ 14 , 34 ].…”

Section: Resultsmentioning

confidence: 99%

“…Whole-cell lysates were used for immunoblotting as described previously [ 14 ]. Cells were lysed using lysis buffer (50 mmol/L Tris-HCl (pH 8.0), 150 mmol/L sodium chloride, 1.0% Triton X-100, 0.5% sodium deoxycholate, 0.1% SDS, protease inhibitor), and 20 μg of protein lysate was resolved by SDS-PAGE and analyzed by immunoblotting with specified antibodies.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cyclizing-berberine A35 induces G2/M arrest and apoptosis by activating YAP phosphorylation (Ser127)

Zhao

Wang

et al. 2018

J Exp Clin Cancer Res

Self Cite

View full text Add to dashboard Cite

BackgroundA35 is a novel synthetic cyclizing-berberine recently patented as an antitumor compound. Based on its dual targeting topoisomerase (top) activity, A35 might overcome the resistance of single-target top inhibitors and has no cardiac toxicity for not targeting top2β. In this study we further explored the biological effects and mechanisms of A35.MethodsAntitumor activity of A35 was evaluated by SRB and colony formation assay. G2/M phase arrest (especially M) and first damage of M-phase cells were investigated by flow cytometry, cytogenetic analysis, immunofluorescence, co-immunoprecipitation and WB. The key role of phospho-YAP (Ser127) in decreasing YAP nuclear localization, subsequent G2/M arrest and proliferation inhibition were explored by YAP1−/− cells, mutated Ser127 YAP construct (Ser127A) and TUNEL.ResultsG2/M arrest induced by A35 was independent of p53. M phase cells at low dose were firstly damaged and most damaged-cells accumulated in M phase, and that was a result of preferring targeting top2α by A35, as top2α is essential to push M phase into next phase, and targeting top2α induced cells arrested at M phase. A35 decreased YAP1 nuclear localization by activating YAP phosphorylation (Ser127) which subsequently regulated the transcription of YAP target genes associated with growth and cycle regulation to induce G2/M arrest and growth inhibition.ConclusionsOur studies suggested the mechanism of G2/M arrest induced by A35 and a novel role of YAP1 (Ser127) in G2/M arrest. As a dual topoisomerase inhibitor characterized by no cardiac toxicity, A35 is a promising topoisomerase anticancer agent and worthy of further development in future.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cyclizing-berberine A35 induces G2/M arrest and apoptosis by activating YAP phosphorylation (Ser127)

Zhao

Wang

et al. 2018

J Exp Clin Cancer Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cell growth inhibition was determined by using a SRB assay [ 11 ]. Cells were seeded in 96-well plates at 4 × 10 3 –8 × 10 3 /well and treated with the increasing concentrations of compound IMB-HDC and incubated for 24 h or 48 h, then cells were fixed with 50% trichloroacetic acid (TCA) (Sigma-Aldrich, Saint Louis, MO, USA), and then 0.4% (w/v) SRB in acetic acid (1%) was added.…”

Section: Methodsmentioning

confidence: 99%

The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation

et al. 2020

View full text Add to dashboard Cite

Sophoridine is a quinolizidine natural product and the exploration of its derivatives has been carried out, and the potent anticancer compound IMB-HDC was acquired. Although previous studies have revealed that some sophoridine derivatives could induce DNA breakage, the underlying mechanisms of inhibition of DNA damage repair (ATR inactivation) and the apoptosis independent of p53, have not been elucidated. Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation. Meanwhile, IMB-HDC that induced the diminished expression of STAT5a target gene contributes to proliferation and leads to apoptosis. More importantly, we give the first evidence that promoting the effect of Tyr694 phosphorylation on nuclear location and subsequent STAT5a target gene transcription depends on Ser780 increased or unchanged phosphorylation and was not correlated with Ser726 phosphorylation.

show abstract

“…Cell growth inhibition was determined using sulforhodamine B (SRB) assay. 9 Cells were seeded in 96-well plates at 4×10 3 –8×10 3 /well, and were treated with increasing concentrations of compound 05D and incubated for 24 or 48 hours. The cells were fixed with 50% trichloroacetic acid (Sigma-Aldrich), and then 0.4% (w/v) SRB in acetic acid (1%) was added.…”

Section: Methodsmentioning

confidence: 99%

Sophoridinol derivative 05D induces tumor cells apoptosis by topoisomerase1-mediated DNA breakage

Zhao

Zhang

et al. 2016

OTT

Self Cite

View full text Add to dashboard Cite

Sophoridine is a quinolizidine natural product of Sophora alopecuroides and has been applied for treatment of malignant trophoblastic tumors. Although characterized by low toxicity, the limited-spectrum antitumor activity hinders its further applications. 05D, a derivative of sophoridine, exhibits a better anticancer activity on diverse cancer cells, including solid tumors, and hematologic malignancy. It could inhibit topoisomerase 1 (top1) activity by stabilizing DNA–top1 complex and induce mitochondria-mediated apoptosis by promoting DNA single- and double-strand breakage mediated by top1. Also, 05D induced HCT116 cells arrest at G1 phase by inactivating CDK2/CDK4–Rb–E2F and cyclinD1–CDK4–p21 checkpoint signal pathways. 05D suppressed the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) activation and decreased 53BP level, which contributed to DNA damage repair, suggesting that the novel compound 05D might be helpful to improve the antitumor activity of DNA damaging agent by repressing ATM and ATR activation and 53BP level. In addition, the priorities in molecular traits and druggability, such as a simple structure and formulation for oral administration, further prove 05D to be a promising targeting topoisomerase agent.

show abstract

Myofibrillogenesis regulator-1 promotes cell adhesion and migration in human hepatoma cells

Cited by 6 publications

References 21 publications

Cyclizing-berberine A35 induces G2/M arrest and apoptosis by activating YAP phosphorylation (Ser127)

Cyclizing-berberine A35 induces G2/M arrest and apoptosis by activating YAP phosphorylation (Ser127)

The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation

Sophoridinol derivative 05D induces tumor cells apoptosis by topoisomerase1-mediated DNA breakage

Contact Info

Product

Resources

About