Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

Wang, Hui‐Chun; Tsai, Yao-Chen; Wu, Yang Chang; Chang, Fang Rong; Liu, Mei Hsin; Chen, Wen Ying; Wu, Chin Chung

doi:10.1371/journal.pone.0037764

Cited by 45 publications

(38 citation statements)

References 37 publications

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“…The HSP70 level increases as bovine embryos develop in vitro [28]. In the present study we found that the coagulansin-A induced the HSP70 expression which is in agreement with a previous report [7], and this protein after inducing in the culture system improves the embryo quality and efficiency.…”

Section: Discussionsupporting

confidence: 93%

“…In the present study supplementation of the IVM medium with coagulansin-A increases the expression of HSP70 which is in agreement with [7]. NF-κB transcription factor is activated by ROS [39].…”

Section: Discussionsupporting

confidence: 89%

“…The variety of activities reported for the extracts, fractions and withanolides isolated from W. coagulans provide promising evidence for future research. Withanolides are also reported to have vital role against cancer and enhance the apoptosis in cancer cells as well as prevent tumorigenesis by inhibiting tumour necrosis factor-α (TNF-α) activated nuclear factor-κB (NF-κB) [5,7]. Clinical and animal research confirmed that withanolide has positive effects in the treatment of Alzheimer's disease, Parkinson's disease and dementia.…”

Section: Introductionmentioning

confidence: 99%

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Coagulansin-A has beneficial effects on the development of bovine embryos in vitro via HSP70 induction

et al. 2016

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SynopsisCoagulansin-A (withanolide) is the steroidal lactone obtained from Withania coagulans which belong to Solanaceae family. The present study investigated the effects of coagulansin-A on bovine oocyte maturation and embryo development in vitro. All these oocytes were aspirated from the ovaries obtained from Korean Hanwoo cows at a local abattoir. To determine whether coagulansin-A has beneficial effects on bovine oocyte maturation in vitro, 355 oocytes per group (control and treated) in seven replicates were subjected with different concentrations (1, 2.5, 5, 7.5 and 10 μM) of coagulansin-A. The coagulansin-A was added in the in vitro maturation (IVM) media followed by in vitro fertilization (IVF) and then in vitro culture (IVC). Only treatment with 5 μM coagulansin-A remarkably (P < 0.05) improved embryos development (Day 8 blastocyst) having 27.30 and 40.01 % for control and coagulansin-A treated groups respectively. Treatment with 5 μM coagulansin-A significantly induced activation of heat shock protein 70 (HSP70) (P < 0.05). Immunofluorescence analysis revealed that 5 μM coagulansin-A treatment also significantly inhibited oxidative stress and inflammation during bovine embryo development in vitro by decreasing 8-oxoguanosine (8-OxoG) (P < 0.05) and nuclear factor-κB (NF-κB) (P < 0.05). The expressions of HSP70 and NF-κB were also conformed through real-time PCR (RT-PCR). Additionally, the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay confirmed that coagulansin-A treatment significantly improved the embryo quality and reduced bovine embryo DNA damage (P < 0.05). The present study provides new information regarding the mechanisms by which coagulansin-A promotes bovine embryo development in vitro.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Coagulansin-A has beneficial effects on the development of bovine embryos in vitro via HSP70 induction

et al. 2016

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“…Secondary metabolic pathway are involved in allelopathic and plant-pathogen interactions and protects plants from herbivores, microorganisms, UV radiation and stress conditions [8]. Withanolides are a large group of steroidal lactones found in Solanaceous plants [9].…”

Section: Introductionmentioning

confidence: 99%

In silico study of binding motifs in squalene synthase enzyme of secondary metabolic pathway solanaceae family

2014

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Solanaceae is an important family with several plants of medicinal importance. These medicinal plants have distinctive pathways for secondary metabolite biosynthesis. In most of the plants, two important compounds, dimethylallyl diphosphate and isopentenyl diphosphate, synthesize isoprenoid or terpenoids. Squalene synthase (SQS) is a key enzyme of the biosynthesis of isoprenoid (farnesyl pyrophosphate (FPP) → squalene). Withania somnifera (ashwagandha), an important medicinal plant of family solanaceae produces withanolides. Withanolides are secondary metabolites synthesized through isoprenoid pathway. In this study, 13 SQS protein sequences from the plants of solanacae family and Arabidopsis thaliana were analyzed. The conserved domains in corresponding sequences were searched. The multiple sequence alignment of conserved domains revealed the important motifs and identified the residue substitution in each motif. Our result further indicated that residue substitution in motifs might not lead to functional variation, although it may affect the binding affinity of Mg(++), FPP and NAD(P)H. In addition, the homology modelling of SQS enzyme of W. somnifera was done for the prediction of three-dimensional structure. Molecular docking study of considered substrates with WsSQS was performed and the docked structure were analyzed further. The docked structures showed binding affinity for motif 2 of WsSQS. Our analysis revealed that 29 residues of motif 2 might be important for catalytic/functional activity of SQS enzyme of W. somnifera. This study may provide an understanding of metabolic pathways responsible for the production of secondary metabolites. The motifs may play a key role in regulating the pathway towards enhanced production of metabolites.

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“…Most of these natural compounds have been safely used for centuries, and their often multitarget nature renders them potential candidates for the development of novel anti-cancer, anti-inflammatory, and antiviral agents [29]. WA, a steroidal lactone, is a bioactive molecule that exhibits potent anticancer activities, compared with other structurally similar withanolides [14,30]. Here we report that WA exhibits strong inhibition of HIV-1 gene expression in an infected T cell model.…”

Section: Discussionmentioning

confidence: 78%

Nf-κb-Dependent Inhibition of HIV-1 Transcription by Withaferin A

Shi¹,

Wilhelm²,

Bell³

et al. 2017

HIV Curr Res

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Despite the remarkable progress made in suppressing HIV-1 infection, antiretroviral drugs are still often inaccessible in developing countries, and there is an urgent need for cheaper and alternative drugs. HIV-1 replication is triggered by the activation of the long terminal repeat (LTR) promoter, which contains two binding sites for the transcription factor nuclear factor κB (NF-κB). Withaferin A (WA), a steroidal lactone isolated from the Indian medicinal plant Withania somnifera, has been found to have significant pharmacological effects on the regulation of immune response. Recent studies have demonstrated that the anti-inflammatory properties of WA are mainly due to its inhibition of the NF-κB pathway. In the present study, we demonstrate that WA represses HIV-1 LTR transcription and viral replication through NF-κB inhibition.The human lymphocyte T cell line Jurkat E6.1 was treated with WA and infected with wild-type pseudotyped HIV-1 particles or mutant viruses containing inactive κB sites. Then, the effect of WA on HIV-1 replication was evaluated by the measurement of reporter activity. Electrophoretic mobility shift assays and Western blots analysis were also performed to study the impact of WA on NF-κB. We found that WA inhibited the transcription of wild-type pseudotyped viruses in single-round infection assays, whereas mutant viruses containing inactive κB sites showed a reduced response to WA. Moreover, we found that WA directly or indirectly inhibits NF-κB nuclear translocation, including RelA and p50 subunits. However, the degradation of inhibitory protein IκB-α was not prevented by WA. Taken together, our results suggest that WA inhibits HIV-1 transcription in human Jurkat E6.1 lymphocyte T cells through the NF-κB pathway.

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Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

Cited by 45 publications

References 37 publications

Coagulansin-A has beneficial effects on the development of bovine embryos in vitro via HSP70 induction

Coagulansin-A has beneficial effects on the development of bovine embryos in vitro via HSP70 induction

In silico study of binding motifs in squalene synthase enzyme of secondary metabolic pathway solanaceae family

Nf-κb-Dependent Inhibition of HIV-1 Transcription by Withaferin A

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