Mifepristone Derivative FZU-00,003 Suppresses Triple-negative Breast Cancer Cell Growth partially via miR-153-KLF5 axis

Liu, Rong; Chen, Haijun; Zhao, Ping; Chen, Chuan-Huizi; Liang, Hongjun; Yang, Chunzhang; Zhou, Zhongmei; Zhi, Xu; Liu, Suling; Chen, Ceshi

doi:10.7150/ijbs.39491

Cited by 15 publications

(9 citation statements)

References 30 publications

(41 reference statements)

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“…However, even at high doses, it has limited anticancer efficacy. To enhance the anticancer activities, a targeted compound chain containing 17 compounds is being designed and synthesized by altering the sensitive metabolic region of mifepristone [74]. Genetic deletion of the PR or its blockade by mifepristone-like progesterone antagonists effectively suppresses the development of high-grade squamous carcinoma (HGSC) of the ovary and its peritoneal metastases.…”

Section: Breast Cancer Ovarian Cancer and Prostatic Cancermentioning

confidence: 99%

Clinical Utility of Mifepristone: Apprising the Expanding Horizons

Karena¹,

Shah²,

Vaghela³

et al. 2022

Cureus

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Mifepristone is a progesterone and glucocorticoid receptor antagonist. Medical abortion with mifepristone and prostaglandin has revolutionized the abortion process extending abortion care to the doors of females. From as low as 2 mg/day to doses extending to 600 mg, from daily dosing to single dosage treatment, mifepristone has a wide perspective in the treatment of various pathologies. Cervical dilatation and myometrial contractility have made the utility of mifepristone feasible for second-trimester termination of pregnancy and induction of labor awaiting Food and Drug Administration approvals. Its anti-progesterone action on the menstrual cycle has a new dimension of use as a contraceptive, as well as use as a menstruation inductive agent. Its role in endometriosis, ectopic pregnancy, and adenomyosis requires more intensive research. Apoptotic action of mifepristone, interference of heterotypic cell adhesion to the basement membrane, cell migration, growth inhibition of various cancer cell lines, decreased epidermal growth factor expression, suppression of invasive and metastatic cancer potential, increase in tumor necrosis factor, downregulation of cyclin-dependent kinase 2, B-cell lymphoma 2, and Nuclear factor kappa B have opened its potential to be explored as anti-cancer treatment and its effects on leiomyoma. The drug needs to be studied more for the prospectus of its anti-glucocorticoid actions in a wider dimension beyond its acquiescence for the treatment of Cushing syndrome.

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Section: Breast Cancer Ovarian Cancer and Prostatic Cancermentioning

confidence: 99%

Clinical Utility of Mifepristone: Apprising the Expanding Horizons

Karena¹,

Shah²,

Vaghela³

et al. 2022

Cureus

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“…KLF5 depletion suppresses BLBC initiation, growth, and metastasis [17,21]. Furthermore, inhibition of KLF5 by mifepristone and its derivatives [22][23][24], metformin [25], mithramycin A [26], super-enhancer inhibitors [27], and the protein arginine N-methyltransferase 5 (PRMT5) inhibitor, PJ-68 [28], suppress BLBC stemness and tumor growth.…”

Section: Ivyspringmentioning

confidence: 99%

Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer

Kong¹,

Ren²,

Fang³

et al. 2022

Int. J. Biol. Sci.

Self Cite

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Basal-like breast cancer (BLBC) accounts for approximately 15% of all breast cancer cases, and patients with BLBC have a low survival rate. Our previous study demonstrated that the KLF5 transcription factor promotes BLBC cell proliferation and tumor growth. In this study, we demonstrated that the histone deacetylase inhibitors (HDACi), suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA), increased KLF5 acetylation at lysine 369 (K369), downregulated KLF5 protein expression levels, and decreased cell viability in BLBC cell lines. HDACi target KLF5 for proteasomal degradation by promoting KLF5 protein ubiquitination. K369 acetylation of KLF5 decreases the binding between KLF5 and its deubiquitinase, BAP1. These findings revealed a novel mechanism by which HDACi suppress BLBC, and a novel crosstalk between KLF5 protein acetylation and ubiquitination.

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“…Also, anti-proliferative activity of miR-153 is mediated by targeting Kruppel-like factor 5 (KLF5) in breast and gastric cancers. KLF5 is a transcription activator of genes involved in proliferation that is activated by the MEK/ERK1/2 signaling pathway (12,30). Moreover, upregulation of other transcription factors such as Zinc finger and BTB domain-containing protein 2 (ZBTB2) and RUNX2 due to downregulation of miR-153 may also affect tumorigenicity of gastric cancer.…”

Section: Role Of Mir-153 In Proliferation Of Cancer Cellsmentioning

confidence: 99%

A comprehensive review on miR-153: Mechanistic and controversial roles of miR-153 in tumorigenicity of cancer cells

Yousefnia

2022

Front. Oncol.

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miRNAs play a crucial role in regulating genes involved in cancer progression. Recently, miR-153 has been mainly well-known as a tumor suppressive miRNA modulating genes in proliferation, metastasis, EMT, angiogenesis and drug resistance ability of a variety types of cancer. Mechanistic activity of miR-153 in tumorigenicity has not been fully reviewed. This manuscript presents a comprehensive review on the tumor suppressive activity of miR-153 as well as introducing the controversial role of miR-153 as an oncogenic miRNA in cancer. Furthermore, it summarizes all potential non-coding RNAs such as long non-coding RNAs (LncRNAs), transcribed ultra-conserved regions (T-UCRs) and circular RNAs (CircRNAs) targeting and sponging miR-153. Understanding the critical role of miR-153 in cell growth, metastasis, angiogenesis and drug resistance ability of cancer cells, suggests miR-153 as a potential prognostic biomarker for detecting cancer as well as providing a novel treatment strategy to combat with several types of cancer.

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Mifepristone Derivative FZU-00,003 Suppresses Triple-negative Breast Cancer Cell Growth partially via miR-153-KLF5 axis

Cited by 15 publications

References 30 publications

Clinical Utility of Mifepristone: Apprising the Expanding Horizons

Clinical Utility of Mifepristone: Apprising the Expanding Horizons

Histone Deacetylase Inhibitors (HDACi) Promote KLF5 Ubiquitination and Degradation in Basal-like Breast Cancer

A comprehensive review on miR-153: Mechanistic and controversial roles of miR-153 in tumorigenicity of cancer cells

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