Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: Combinational approach for enhanced differentiation

Shah, Navjot; Kataria, Hardeep; Kaul, Sunil C.; Ishii, Tetsuro; Kaur, Gurcharan; Wadhwa, Renu

doi:10.1111/j.1349-7006.2009.01236.x

Cited by 92 publications

(54 citation statements)

References 48 publications

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“…The cells were stained with anti-VEGF and -hnRNP-K antibodies (Santa Cruz Biotech), as described previously (7,9).…”

Section: Immunostainingmentioning

confidence: 99%

“…Furthermore, bioinformatics and experimental data suggested the differential binding efficacies of withaferin A and withanone to cellular targets including mortalin, p53, p21, and NRF2 (8). We had earlier reported that the low dose of alcoholic extract of ashwagandha leaves (i-Extract) and its components, withanone and withaferin A, were nontoxic and instead induced differentiation in glioma cells (9). Hence, in low dose, they were proposed as useful in differentiation-based milder and effective glioma therapy.…”

Section: Introductionmentioning

confidence: 99%

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Withanone-Rich Combination of Ashwagandha Withanolides Restricts Metastasis and Angiogenesis through hnRNP-K

Gao

Shah

Lee

et al. 2014

Molecular Cancer Therapeutics

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Ashwagandha is an important herb used in the Indian system of traditional home medicine, Ayurveda. Alcoholic extract (i-Extract) from its leaves and its component, withanone, were previously shown to possess anticancer activity. In the present study, we developed a combination of withanone and withaferin A, major withanolides in the i-Extract, that retained the selective cancer cell killing activity and found that it also has significant antimigratory, -invasive, and -angiogenic activities, in both in vitro and in vivo assays. Using bioinformatics and biochemical approaches, we demonstrate that these phytochemicals caused downregulation of migration-promoting proteins hnRNP-K, VEGF, and metalloproteases and hence are candidate natural drugs for metastatic cancer therapy. Mol Cancer Ther; 13(12); 2930-40. Ó2014 AACR.

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“…The cells were stained with anti-VEGF and -hnRNP-K antibodies (Santa Cruz Biotech), as described previously (7,9).…”

Section: Immunostainingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Withanone-Rich Combination of Ashwagandha Withanolides Restricts Metastasis and Angiogenesis through hnRNP-K

Gao

Shah

Lee

et al. 2014

Molecular Cancer Therapeutics

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“…Studies have shown that therapeutic doses of WA exert anti-cancer, anti-inflammatory, and anti-angiogenesis effects [9,16,[39][40][41]. Our results suggest that WA, a bioactive compound derived from Indian Ashwagandha, disrupts viral gene expression through the inhibition of NF-κB activation.…”

Section: Limitations and Clinical Implicationsmentioning

confidence: 50%

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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“…Withaferin A is one of the most predominant compounds among the withanolides. Previous studies have reported various biological activities of the crude root 15 and leaf extracts [16][17][18] of W. somnifera. Withaferin A, an abundant withanolide, has potent anticancer and anti-proliferative activities against a wide range of cancer cell types [19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Exploring the inhibitory activity of Withaferin-A against Pteridine reductase-1 of L. donovani

Chandrasekaran

Veronica

Gundampati

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Withaferin A is an abundant withanolide present in Withania somnifera leaves and to some extent in roots. It has been known for its profound anti-cancer properties, but its role in counteracting the Leishmania donovani infection has to be explored. Pteridine reductase 1 (PTR1) is involved in pteridine salvage and an important enzyme for the parasite growth, which could be targeted for the development of an efficient antileishmanial drug. We employed molecular docking studies to identify the binding mode of withaferin A with PTR1 in silico. We further cloned, expressed, and purified PTR1 of L. donovani and performed the enzyme kinetics using the Michaelis-Menten equation and enzyme inhibition studies with withaferin A by plotting the Lineweaver-Burk graph, which followed an uncompetitive mode of inhibition. We also showed the inhibition of the enzyme in the crude lysate of treated parasites. Thus, our study contributes towards understanding the mode of action of withaferin A against L. donovani parasite.

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Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: Combinational approach for enhanced differentiation

Cited by 92 publications

References 48 publications

Withanone-Rich Combination of Ashwagandha Withanolides Restricts Metastasis and Angiogenesis through hnRNP-K

Withanone-Rich Combination of Ashwagandha Withanolides Restricts Metastasis and Angiogenesis through hnRNP-K

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

Exploring the inhibitory activity of Withaferin-A against Pteridine reductase-1 of L. donovani

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