A novel histone deacetylase inhibitor LT-548-133-1 induces apoptosis by inhibiting HDAC and interfering with microtubule assembly in MCF-7 cells

Xue, Jinbing; Wu, Gang; Ejaz, Umer; Akhtar, Fahad; Wan, Xinyu; Geng, Aixing; Chen, Yadong; He, Siyu

doi:10.1007/s10637-021-01102-9

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…This disrupts chromosome separation during mitosis and ultimately leads to CIN. Previous studies have reported similar spindle structures, 40–43 and demonstrated that elevated BUB1 expression in lymphoma cells causes aneuploidy through excessive activation of Aurora B kinase 60 . These findings support our observations on BUB1's role in CIN and emphasize the importance of regulating its expression for mitotic progression.…”

Section: Discussionsupporting

confidence: 92%

“…However, in BUB1‐WT cells, spindle formation was disrupted and asymmetric spindle including monopolar spindles was observed, thus leading to aberrant chromosome segregation. Similar findings have been reported in previous studies conducted by other researchers 40–43 . Next, the impact of BUB1 knockdown on abnormal nuclear morphology was investigated by Giemsa staining.…”

Section: Resultssupporting

confidence: 85%

“…Similar findings have been reported in previous studies conducted by other researchers. 40 , 41 , 42 , 43 Next, the impact of BUB1 knockdown on abnormal nuclear morphology was investigated by Giemsa staining. The presence of nucleoplasmic bridges (NPB), nuclear buds (NBUD) and micronucleus (MN), indicators of CIN, 44 reduced in the 8505C cells with BUB1 knockdown (Figure 6E ).…”

Section: Resultsmentioning

confidence: 99%

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BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability

Jin,

Ding,

Chen

et al. 2024

J Cellular Molecular Medi

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Chromosome instability (CIN) is a common contributor driving the formation and progression of anaplastic thyroid cancer (ATC), but its mechanism remains unclear. The BUB1 mitotic checkpoint serine/threonine kinase (BUB1) is responsible for the alignment of mitotic chromosomes, which has not been thoroughly studied in ATC. Our research demonstrated that BUB1 was remarkably upregulated and closely related to worse progression‐free survival. Knockdown of BUB1 attenuated cell viability, invasion, migration and induced cell cycle arrests, whereas overexpression of BUB1 promoted the cell cycle progression of papillary thyroid cancer cells. BUB1 knockdown remarkably repressed tumour growth and tumour formation of nude mice with ATC xenografts and suppressed tumour metastasis in a zebrafish xenograft model. Inhibition of BUB1 by its inhibitor BAY‐1816032 also exhibited considerable anti‐tumour activity. Further studies showed that enforced expression of BUB1 evoked CIN in ATC cells. BUB1 induced CIN through phosphorylation of KIF14 at serine1292 (Ser1292). Overexpression of the KIF14ΔSer1292 mutant was unable to facilitate the aggressiveness of ATC cells when compared with that of the wild type. Collectively, these findings demonstrate that the BUB1/KIF14 complex drives the aggressiveness of ATC by inducing CIN.

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Section: Discussionsupporting

confidence: 92%

Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

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BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability

Jin,

Ding,

Chen

et al. 2024

J Cellular Molecular Medi

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“…It is well documented that exposure to microtubule targeting agents leads to the malformed mitotic spindle which eventually leads to cell cycle arrest at the G2/M phase and apoptosis induction [ 27 ]. Thus, the effect of the selected candidate 9 on the cell cycle progression of the HepG2 cell line was examined by flow cytometry analysis (FACS).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents

et al. 2022

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A group of novel trimethoxyphenyl (TMP)-based analogues were synthesized by varying the azalactone ring of 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxybenzylidene)oxazolone 1 and characterized using NMR spectral data as well as elemental microanalyses. All synthesized compounds were screened for their cytotoxic activity utilizing the hepatocellular carcinoma (HepG2) cell line. Compounds 9, 10 and 11 exhibited good cytotoxic potency with IC50 values ranging from 1.38 to 3.21 μM compared to podophyllotoxin (podo) as a reference compound. In addition, compounds 9, 10 and 11 exhibited potent inhibition of β-tubulin polymerization. DNA flow cytometry analysis of compound 9 shows cell cycle disturbance at the G2/M phase and a significant increase in Annexin-V-positive cells compared with the untreated control. Compound 9 was further studied regarding its apoptotic potential in HepG2 cells; it decreased the level of MMP and Bcl-2 as well as boosted the level of p53 and Bax compared with the control HepG2 cells.

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“…In breast cancer, HDAC1, HDAC6, and HDAC11 can increase the transcription and expression levels of CDK1, cyclin-A, and cyclin-B by the deacetylation of H3K27 and H3K9, can inhibit the transcription of P21, and promote G2/M transformation by inhibiting the acetylation of histones in the specificity protein 1 (SP1)/specificity protein 3 (SP3) regions of P21. These effects reduce the proportion of G2/M cells and sensitivity to radiotherapy ( 100 , 106 – 108 ).…”

Section: Hdacs and Radiotherapy Resistancementioning

confidence: 99%

HDAC-an important target for improving tumor radiotherapy resistance

et al. 2023

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Radiotherapy is an important means of tumor treatment, but radiotherapy resistance has been a difficult problem in the comprehensive treatment of clinical tumors. The mechanisms of radiotherapy resistance include the repair of sublethal damage and potentially lethal damage of tumor cells, cell repopulation, cell cycle redistribution, and reoxygenation. These processes are closely related to the regulation of epigenetic modifications. Histone deacetylases (HDACs), as important regulators of the epigenetic structure of cancer, are widely involved in the formation of tumor radiotherapy resistance by participating in DNA damage repair, cell cycle regulation, cell apoptosis, and other mechanisms. Although the important role of HDACs and their related inhibitors in tumor therapy has been reviewed, the relationship between HDACs and radiotherapy has not been systematically studied. This article systematically expounds for the first time the specific mechanism by which HDACs promote tumor radiotherapy resistance in vivo and in vitro and the clinical application prospects of HDAC inhibitors, aiming to provide a reference for HDAC-related drug development and guide the future research direction of HDAC inhibitors that improve tumor radiotherapy resistance.

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A novel histone deacetylase inhibitor LT-548-133-1 induces apoptosis by inhibiting HDAC and interfering with microtubule assembly in MCF-7 cells

Cited by 7 publications

References 25 publications

BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability

BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability

Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents

HDAC-an important target for improving tumor radiotherapy resistance

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