Synthesis and biological activity of selenopsammaplin A and its analogues as antitumor agents with DOT1L inhibitory activity

Han, H.‐J.; Byun, Woong Sub; Lee, Gyu Ho; Kim, Won Kyung; Jang, Kyungkuk; Yang, Sehun; Yang, Jewon; Ha, Min Woo; Hong, Suckchang; Lee, Jeeyeon; Shin, Jongheon; Oh, Ki Bong; Lee, Sang Kook; Park, Hyeung‐geun

doi:10.1016/j.bmc.2021.116072

Cited by 8 publications

(3 citation statements)

References 41 publications

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“…33 This may be associated with the downregulated expression of Nanog. In addition, PsA also shows anticancer activity by inducing cell cycle arrest and apoptosis, 10,11,34,35 consistent with the decreased expression of Nanog and BCL2L1 in our study.…”

Section: Discussionsupporting

confidence: 88%

PsA inhibits the development of bovine embryos through epigenetic and oxidative stress

Zhan

et al. 2023

ajvr

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OBJECTIVE Histone deacetylases (HDACs) are the key regulators involved in the process of embryo development and tumor progression and are often dysregulated in numerous disordered cells, including tumor cells and somatic cell nuclear transfer (SCNT) embryos. Psammaplin A (PsA), a natural small-molecular therapeutic agent, is a potent histone deacetylase inhibitor (HDACi) that alters the regulation of histone. SAMPLES Approximately 2,400 bovine parthenogenetic (PA) embryos. PROCEDURES To investigate the effect of PsA on bovine preimplanted embryos, we analyzed the preimplantation development of PA embryos treated with PsA in this study. RESULTS The blastocyst formation rate of bovine PA embryos decreased sharply with an increase in concentration and duration. Furthermore, the expression of the pluripotency-related gene Nanog was decreased, and the inhibitory effects on histone deacetylases 1 (HDAC1) and DNA methylation transferase 1 (DNMT1) were observed in bovine PA embryos. The acetylation level of histone H3 lysine 9 (H3K9) was enhanced by a PsA treatment of 10 μM for 6 h, while the DNA methylation appeared unchanged. Interestingly, we also found that PsA treatment enhanced the intracellular reactive oxygen species (ROS) generation and decreased the intracellular mitochondrial membrane potential (MMP)- and superoxide dismutase 1 (SOD1)-induced oxidative stress. Our findings improve the understanding of HDAC in embryo development and provide a theoretical basis and reproduction toxicity evaluation for the application of PsA. CLINICAL RELEVANCE These results indicate that PsA inhibits the development of bovine preimplantation PA embryos, supplying data for the PsA clinical application concentration to avoid reproductive toxicity. In addition, the reproduction toxic effect of PsA may be modulated through increased oxidative stress on the bovine PA embryo, suggesting that PsA in combination with antioxidants, for example, melatonin, might be an effective clinical application strategy.

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Section: Discussionsupporting

confidence: 88%

PsA inhibits the development of bovine embryos through epigenetic and oxidative stress

Zhan

et al. 2023

ajvr

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“…Numerous studies have reported potential therapeutic benefits from selenium supplementation or the use of selenium-derived compounds in breast cancers [ 131 , 132 , 133 , 134 ]. There are limited available treatments for triple-negative breast cancer (TNBC) patients, especially since these types of patients tend to develop chemoresistance [ 135 ].…”

Section: Role Of Selenium and Its Therapeutic Advantages In Various C...mentioning

confidence: 99%

Therapeutic Benefits of Selenium in Hematological Malignancies

Ehudin

Golla

Trivedi

et al. 2022

IJMS

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Supplementing chemotherapy and radiotherapy with selenium has been shown to have benefits against various cancers. This approach has also been shown to alleviate the side effects associated with standard cancer therapies and improve the quality of life in patients. In addition, selenium levels in patients have been correlated with various cancers and have served as a diagnostic marker to track the efficiency of treatments or to determine whether these selenium levels cause or are a result of the disease. This concise review presents a survey of the selenium-based literature, with a focus on hematological malignancies, to demonstrate the significant impact of selenium in different cancers. The anti-cancer mechanisms and signaling pathways regulated by selenium, which impart its efficacious properties, are discussed. An outlook into the relationship between selenium and cancer is highlighted to guide future cancer therapy development.

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“…Metastasis is responsible for almost 90% of cancer-related deaths, and BC is one of the most metastatic cancers, with metastasis rates reaching approximately 40% [43]. Moreover, metastatic potential increases when cancer cells acquire resistance [44].…”

Section: Effects Of Pulvomycin On Cell Invasion Migration and Epithelial-mesenchymal Transition In Mda-mb-231-dtr Cellsmentioning

confidence: 99%

Antitumor Activity of Pulvomycin via Targeting Activated-STAT3 Signaling in Docetaxel-Resistant Triple-Negative Breast Cancer Cells

et al. 2021

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Although docetaxel-based regimens are common and effective for early-stage triple-negative breast cancer (TNBC) treatment, acquired drug resistance frequently occurs. Therefore, a novel therapeutic strategy for docetaxel-resistant TNBC is urgently required. Signal transducer and activator of transcription 3 (STAT3) plays a pivotal role in the tumorigenesis and metastasis of numerous cancers, and STAT3 signaling is aberrantly activated in TNBC cells. In this study, a docetaxel-resistant TNBC cell line (MDA-MB-231-DTR) was established, and mechanisms for the antitumor activity of pulvomycin, a novel STAT3 inhibitor isolated from marine-derived actinomycete, were investigated. Levels of activated STAT3 (p-STAT3 (Y705)) increased in docetaxel-resistant cells, and knockdown of STAT3 recovered the sensitivity to docetaxel in MDA-MB-231-DTR cells. Pulvomycin effectively inhibited the proliferation of both cell lines. In addition, pulvomycin suppressed the activation of STAT3 and subsequently induced G0/G1 cell cycle arrest and apoptosis. Pulvomycin also significantly inhibited the invasion and migration of MDA-MB-231-DTR cells through the modulation of epithelial-mesenchymal transition markers. In an MDA-MB-231-DTR-bearing xenograft mouse model, the combination of pulvomycin and docetaxel effectively inhibited tumor growth through STAT3 regulation. Thus, our findings demonstrate that the combination of docetaxel and STAT3 inhibitors is an effective strategy for overcoming docetaxel resistance in TNBC.

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Synthesis and biological activity of selenopsammaplin A and its analogues as antitumor agents with DOT1L inhibitory activity

Cited by 8 publications

References 41 publications

PsA inhibits the development of bovine embryos through epigenetic and oxidative stress

PsA inhibits the development of bovine embryos through epigenetic and oxidative stress

Therapeutic Benefits of Selenium in Hematological Malignancies

Antitumor Activity of Pulvomycin via Targeting Activated-STAT3 Signaling in Docetaxel-Resistant Triple-Negative Breast Cancer Cells

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