Histone deacetylase inhibitor, AR‐42, exerts antitumor effects by inducing apoptosis and cell cycle arrest in Y79 cells

Duan, Sujuan; Gong, Xiaona; Liu, Xing; Cui, Wenwen; Chen, Kaddie; Mao, Longbing; Sun, Jun; Zhou, Ruihao; Sang, Yi

doi:10.1002/jcp.28806

Cited by 5 publications

(2 citation statements)

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“…The cyclic peptide HDAC inhibitor romidepsin induces cell cycle arrest and apoptosis by increasing the acetylation of BCL6 [40]. Finally, the fatty acid HDAC inhibitor AR-42 induces cell cycle arrest and apoptosis by inhibiting the AKT/NFκB pathway [41]. Unlike DNMTIs, HDAC inhibitor monotherapy offers low clinical efficacy, achieving poor overall response in AML.…”

Section: Therapeutics Targeting Modifications In Histone Tailsmentioning

confidence: 99%

Advances in Epigenetic Cancer Therapeutics

Hillyar¹,

Rallis²,

Varghese³

2020

Cureus

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Cancer has traditionally been hailed a genetic disease, dictated by successive genetic aberrations which alter gene expression. Yet, recent advances in molecular sequencing technologies, enabling the characterisation of cancer patient phenotypes on a large scale, have highlighted epigenetic changes as a hallmark of cancer. Epigenetic modifications, including DNA methylation and demethylation and histone modifications, have been found to play a key role in the pathogenesis of a wide variety of cancers through the regulation of chromatin state, gene expression and other nuclear events. Targeting epigenetic aberrations offers remarkable promise as a potential anti-cancer therapy given the reversible nature of epigenetic changes. Hence, epigenetic therapy has emerged as a rapidly advancing field of cancer research. A plethora of epigenetic therapies which inhibit enzymes of post-translational histone modifications, so-called 'writers', 'erasers' and 'readers', have been developed, with several epigenetic inhibitor agents approved for use in routine clinical practice. Epigenetic therapeutics inhibit the methylation or demethylation and acetylation or deacetylation of DNA and histone proteins. Their targets include writers (DNA methyltransferases [DNMT], histone acetyltransferases [HAT] and histone deacetylases [HDAC]) and erasers (histone demethylases [HDM] and histone methylases [HMT]). With new epigenetic mechanisms increasingly being elucidated, a vast array of targets and therapeutics have been brought to the fore. This review discusses recent advances in cancer epigenetics with a focus on molecular targets and mechanisms of action of epigenetic cancer therapeutics.

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Section: Therapeutics Targeting Modifications In Histone Tailsmentioning

confidence: 99%

Advances in Epigenetic Cancer Therapeutics

Hillyar¹,

Rallis²,

Varghese³

2020

Cureus

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“…RT-PCR was performed as previously described. [29] In brief, total RNA was extracted by TRIzol reagent (Invitrogen, #15596026)from each sample 4 days after siRNA transfection, and cDNA was obtained using a PrimeScript™ RT reagent kit (Takara, #RR037B) according to the manufacturer's protocol. All RT-PCR was performed with SYBR GREEN reagents with a CFX96 Real-Time System (BIO-RAD, CFX96 optics module).…”

Section: Real-time Polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Retinoblastoma ( Rb ) promotes senescence of corneal endothelial cells by inhibiting the activation of E2F2

Jiang¹,

l²,

Duan³

et al. 2020

Preprint

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Background Senescence-like changes occur in aging Corneal endothelial cells (CECs), and these changes are associated with decreased vision and age-related corneal diseases. such as Fuchs endothelial dystrophy (FED), chronic corneal allograft dysfunction (CCAD). Such changes have also been shown to cultured cell in vitro after passaging. Therefore, studying the mechanism of CEC senescence would aid in the development of anti-senescence treatment, which would benefit FED and CCAD. The tumor suppressor retinoblastoma (RB) gene product pRB triggers senescent growth arrest when inactivated. In this study, we used siRNA treatment to evaluate whether RB knockdown could suppress CEC senescence, and we investigated relevant molecular mechanisms.Methods RCECs were obtained and were cultured with or without siRb. Senescent cells were detected with a β-galactosidase senescence staining kit. The gene p21, which is associated with a senescent phenotype, was measured by RT-PCR. The morphology and migration of cultured RCECs were examined by phase-contrast microscopy. ZO-1 and N-Cadherin, which are involved in pump and barrier functions, were assessed by immunofluorescence. Cell cycle assessment was performed using a flow cytometer (BD FACSCalibur).Results As the cells were passaged, the number of senescent RCECs, the levels of the senescence-related gene p21, and the levels of senescence-associated secretory factors increased. SiRNA-mediated knockdown of RB led to suppression of cell senescence and the SASP. Furthermore, RB intervention increased the numbers of cells at the G2/M and S phase but did not influence the cell function or migratory ability. Knockdown of RB promoted the activation of E2F2.Conclusions We demonstrated that as the cells increased in passage number, the number of senescent RCECs, the levels of the senescence-related genes p21, and the levels of senescence-associated secretory factors increased. Retinoblastoma (Rb) promoted the senescence of corneal endothelial cells by inhibiting the activation of E2F2.

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