Valtrate from <i>Valeriana jatamansi Jones</i> induces apoptosis and inhibits migration of human breast cancer cells <i>in vitro</i>

Tian, Shasha; Wang, Zhizi; Wu, Zeqi; Wei, Yingying; Yang, Bo; Lou, Siyue

doi:10.1080/14786419.2018.1548454

Cited by 24 publications

(19 citation statements)

References 16 publications

(4 reference statements)

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“…Oridonin, a natural tetracycline diterpenoid, isolated from Rabdosia rubescens, suppresses cell proliferation and increases G2/M cell cycle arrest via inhibiting PI3K-Akt pathway and upregulating p21 and p53 in cancer cells such as in esophageal cancer [82] and oral squamous cell carcinoma cells [83]. Deguelin treatment in human gastric cancer cells [84], β-2-himachalen-6-ol treatment of skin carcinogenesis mouse model [85], Valtrate treatment in human breast cancer cells [86] and Aloperine treatment in prostate cancer cells [87] reduce tumor growth and cell survival by inhibiting PI3K-Akt pathway and upregulating p21 expression. Chemicals that have been shown to induce p21 expression in cancer research are listed in Table 2.…”

Section: P21 As a Target In Cancer Treatmentmentioning

confidence: 99%

p21 in Cancer Research

Shamloo

Usluer

2019

Cancers

251

139

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p21 functions as a cell cycle inhibitor and anti-proliferative effector in normal cells, and is dysregulated in some cancers. Earlier observations on p21 knockout models emphasized the role of this protein in cell cycle arrest under the p53 transcription factor activity. Although tumor-suppressor function of p21 is the most studied aspect of this protein in cancer, the role of p21 in phenotypic plasticity and its oncogenic/anti-apoptotic function, depending on p21 subcellular localization and p53 status, have been under scrutiny recently. Basic science and translational studies use precision gene editing to manipulate p21 itself, and proteins that interact with it; these studies have led to regulatory/functional/drug sensitivity discoveries as well as therapeutic approaches in cancer field. In this review, we will focus on targeting p21 in cancer research and its potential in providing novel therapies.

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Section: P21 As a Target In Cancer Treatmentmentioning

confidence: 99%

p21 in Cancer Research

Shamloo

Usluer

2019

Cancers

251

139

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“…Valerian ( Valeriana officinalis ), a member of Valerianaceae family, is a perennial herb 4 and has been authorized by the US Food and Drug Administration (FDA) as a complementary and alternative medicine (CAM) to treat insomnia and other sleep-related disorders. 5 Valerian has been found to have anticancer effect for liver cancer, 6 and its extraction compounds, such as iridoids, Valepotriates, and F3, have been shown as promising antitumor agents in many types of cancer, 7 , 8 , 9 which warrants further exploration to discover novel active compounds from valerian for cancer treatment. 10 …”

Section: Introductionmentioning

confidence: 99%

Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor

Han

Nusbaum

Chen

et al. 2020

Molecular Therapy - Oncolytics

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Liver cancer is the fastest growing cause of cancer deaths in the United States due to its aggressiveness and lack of effective therapies. The current preclinical study examines valeric acid (pentanoic acid [C 5 H 10 O 2 ]), one of the main compounds of valerian root extract, for its therapeutic use in liver cancer treatment. Anticancer efficacy of valeric acid was tested in a series of in vitro assays and orthotopic xenograft mouse models. The molecular target of valeric acid was also predicted, followed by functional confirmation. Valeric acid has a broad spectrum of anticancer activity with specifically high cytotoxicity for liver cancer in cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation assays. Mouse models further demonstrate that systematic administration of lipid-based nanoparticle-encapsulated valeric acid significantly reduces the tumor burden and improves survival rate. Histone deacetylase (HDAC)-inhibiting functions of valeric acid are also revealed by a structural target prediction tool and HDAC activity assay. Further transcriptional profiling and network analyses illustrate that valeric acid affects several cancer-related pathways that may induce apoptosis. In summary, we demonstrate for the first time that valeric acid suppresses liver cancer development by acting as a potential novel HDAC inhibitor, which warrants further investigation on its therapeutic implications.

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“…As a member of valepotriates, AVT is active against sleeping disorder and other neurological diseases 14 , however, there are very few studies on AVT in its anti-cancer activities. In contrast to valtrate that has been reported with specific activities against breast and ovarian cancers 15 , there are only two reports regarding AVT for its anti-oxidant and its cytotoxic activities 10,16 .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis

Sun

Yan²,

Xu³

et al. 2020

Preprint

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Background : The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis. Methods: A luciferase assay was applied to screen potential inhibitors of the Otub1/c-Maf axis. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity. Results: acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against Otub1/c-Maf/luciferase. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity. Conclusions: The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment.

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Valtrate from Valeriana jatamansi Jones induces apoptosis and inhibits migration of human breast cancer cells in vitro

Cited by 24 publications

References 16 publications

p21 in Cancer Research

p21 in Cancer Research

Valeric Acid Suppresses Liver Cancer Development by Acting as a Novel HDAC Inhibitor

Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis

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