HDAC inhibitor cowanin extracted from G. fusca induces apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathways in Jurkat cells

Punpai, Sakdiphong; Saenkham, Audchara; Jarintanan, Faongchat; Jongrungruangchok, Suchada; Choowongkomon, Kiattawee; Suksamrarn, Sunit; Tanechpongtamb, Wanlaya

doi:10.1016/j.biopha.2021.112577

Cited by 13 publications

(6 citation statements)

References 55 publications

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“…36 HDAC inhibitors also inhibit the PI3K/Akt/mTOR signaling pathway, leading to autophagy activation. 37 Besides, HDAC1 and HDAC2 are reported to regulate metabolic ROS production and play protective roles in various tissues and organs by inhibiting inflammatory responses. 38,39 However, the roles of HDAC in the pathogenesis and treatment of SLI have not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition

Fan,

Zhao,

Zhu

et al. 2024

Food Funct.

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Section: Discussionmentioning

confidence: 99%

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition

Fan,

Zhao,

Zhu

et al. 2024

Food Funct.

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“…Consequently, the HDACi treatment only relieved a portion of the post-transcriptional blocks. However, since certain HDACi induce autophagy in T-cells ( 69 ), this might also explain the discrepancy between increased tax mRNA and only moderately enhanced Tax protein levels, which has to be addressed in future studies. Further agents are required to alleviate other barriers (completion of transcription, multiple splicing, translation) to retroviral reactivation in combination with HDACi treatment.…”

Section: Discussionmentioning

confidence: 99%

HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients’ T-cells

et al. 2022

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The viral transactivator Tax plays a key role in HTLV-1 reactivation and de novo infection. Previous approaches focused on the histone deacetylase inhibitor (HDACi) Valproate as a latency-reversing agent to boost Tax expression and expose infected cells to the host’s immune response. However, following treatment with Valproate proviral load decreases in patients with HAM/TSP were only transient. Here, we hypothesize that other compounds, including more potent and selective HDACi, might prove superior to Valproate in manipulating Tax expression. Thus, a panel of HDACi (Vorinostat/SAHA/Zolinza, Panobinostat/LBH589/Farydak, Belinostat/PXD101/Beleodaq, Valproate, Entinostat/MS-275, Romidepsin/FK228/Istodax, and MC1568) was selected and tested for toxicity and potency in enhancing Tax expression. The impact of the compounds was evaluated in different model systems, including transiently transfected T-cells, chronically HTLV-1-infected T-cell lines, and freshly isolated PBMCs from HTLV-1 carriers ex vivo. We identified the pan-HDACi Panobinostat and class I HDACi Romidepsin as particularly potent agents at raising Tax expression. qRT-PCR analysis revealed that these inhibitors considerably boost tax and Tax-target gene transcription. However, despite this significant increase in tax transcription and histone acetylation, protein levels of Tax were only moderately enhanced. In conclusion, these data demonstrate the ability of Panobinostat and Romidepsin to manipulate Tax expression and provide a foundation for further research into eliminating latently infected cells. These findings also contribute to a better understanding of conditions limiting transcription and translation of viral gene products.

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“…Two active chemicals isolated from G. fusca have been evaluated for their therapeutic potential in the context of hematological malignancies. Cowaxanthone (Figure 6), one of the xanthone families derived from G. fusca, displayed anticancer properties by inducing apoptosis in leukemic T-cells via downregulation of HDACs activity [109]. However, cowaxanthone was less hazardous to normal Vero cells.…”

Section: Cowaxanthone and Cowainmentioning

confidence: 99%

Potential of Synthetic and Natural Compounds as Novel Histone Deacetylase Inhibitors for the Treatment of Hematological Malignancies

Pal

Raj

Nandi

et al. 2023

Cancers

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Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that remove or add acetyl groups to lysine residues of histones, respectively. Histone deacetylation causes DNA to more snugly encircle histones and decreases gene expression, whereas acetylation has the opposite effect. Through these small alterations in chemical structure, HATs and HDACs regulate DNA expression. Recent research indicates histone deacetylase inhibitors (HDACis) may be used to treat malignancies, including leukemia, B-cell lymphoma, virus-associated tumors, and multiple myeloma. These data suggest that HDACis may boost the production of immune-related molecules, resulting in the growth of CD8-positive T-cells and the recognition of nonreactive tumor cells by the immune system, thereby diminishing tumor immunity. The argument for employing epigenetic drugs in the treatment of acute myeloid leukemia (AML) patients is supported by evidence that both epigenetic changes and mutations in the epigenetic machinery contribute to AML etiology. Although hypomethylating drugs have been licensed for use in AML, additional epigenetic inhibitors, such as HDACis, are now being tested in humans. Preclinical studies evaluating the efficacy of HDACis against AML have shown the ability of specific agents, such as anobinostat, vorinostat, and tricostatin A, to induce growth arrest, apoptosis, autophagy and cell death. However, these inhibitors do not seem to be successful as monotherapies, but instead achieve results when used in conjunction with other medications. In this article, we discuss the mounting evidence that HDACis promote extensive histone acetylation, as well as substantial increases in reactive oxygen species and DNA damage in hematological malignant cells. We also evaluate the potential of various natural product-based HDACis as therapeutic agents to combat hematological malignancies.

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HDAC inhibitor cowanin extracted from G. fusca induces apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathways in Jurkat cells

Cited by 13 publications

References 55 publications

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition

Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition

HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients’ T-cells

Potential of Synthetic and Natural Compounds as Novel Histone Deacetylase Inhibitors for the Treatment of Hematological Malignancies

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