Functional Characterisation of Anticancer Activity in the Aqueous Extract of Helicteres angustifolia L. Roots

Li, Kejuan; Yu, Yue; Sun, Sujuan; Liu, Ye; Garg, Sukant; Kaul, Sunil C.; Lei, Zhongfang; Gao, Ran; Wadhwa, Renu; Zhang, Zhenya

doi:10.1371/journal.pone.0152017

Cited by 18 publications

(22 citation statements)

References 33 publications

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“…45 The extent of DNA damage was calculated as percent DNA in the tail using OpenComet (v1.3), a plugin for the image processing program ImageJ. The study was repeated independently three times.…”

Section: Methodsmentioning

confidence: 99%

Withaferin-A kills cancer cells with and without telomerase: chemical, computational and experimental evidences

Katiyar

Sundar

et al. 2017

Cell Death Dis

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Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers). Withaferin-A (Wi-A), a major constituent of the medicinal plant, Withania somnifera (Ashwagandha), has been shown to exert anti-tumour activity. However, its effect on either telomerase or ALT mechanisms has not been investigated. Here, by using isogenic cancer cells with/without telomerase, we found that Wi-A caused stronger cytotoxicity to ALT cells. It was associated with inhibition of ALT-associated promyelocytic leukemia nuclear bodies, an established marker of ALT. Comparative analyses of telomerase positive and ALT cells revealed that Wi-A caused stronger telomere dysfunction and upregulation of DNA damage response in ALT cells. Molecular computational and experimental analyses revealed that Wi-A led to Myc-Mad mediated transcriptional suppression of NBS-1, an MRN complex protein that is an essential component of the ALT mechanism. The results suggest that Wi-A could be a new candidate drug for ALT cancers.

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Section: Methodsmentioning

confidence: 99%

Withaferin-A kills cancer cells with and without telomerase: chemical, computational and experimental evidences

Katiyar

Sundar

et al. 2017

Cell Death Dis

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“…After the mixture was filtered by Whatman paper (No.1), the filtrate was centrifuged at 3500 RMP for 15 min. The supernatant was evaporated at a temperature 40°C for 24 h and the acquired powder (46.5% and 46.5 g of root powder) was maintained at −20°C until utilized (Roghani et al, 2007;Li et al, 2016).…”

Section: Plant and Extractmentioning

confidence: 99%

Effects of Arctium lappa aqueous extract on lipid profile and hepatic enzyme levels of sucrose-induced metabolic syndrome in female rats

Ahangarpour

Aliakbari

Mohaghegh

et al. 2016

Braz. J. Pharm. Sci.

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Arctium lappa is known to have antioxidant and antidiabetic effects in traditional medicine. Objectives: The aim of this paper was to study the effects of A. lappa root extract (AE) on lipid profile and hepatic enzyme levels in sucrose-induced metabolic syndrome (MS) in female rats. The study used 40 adult female Wistar rats weighing 150 g-250 g randomly divided into five groups: control, metabolic syndrome (MS), metabolic syndrome+AE at 50,100, 200 mg/kg. MS was induced by administering 50% sucrose in drinking water for 6 weeks. AE was intra-peritoneally administered daily at doses of 50,100, and 200 mg/kg for two sequential weeks at the end of the fourth week in metabolic syndrome rats. Twenty-four hours after the last administration of AE, blood was collected and centrifuged, and then the serum was used for the measurement of lipid profile and hepatic enzyme. Serum glucose, insulin, fasting insulin resistance index, body weight, water intake, lipid profile, and hepatic enzymes were significantly increased although food intake was decreased in MS rats compared to the control rats. The lipids and liver enzymes were reduced by AE extracts in the MS group. This study showed that the A. lappa root aqueous extract exhibits a hypolipidemic activity of hyperlipidemic rats. This activity is practically that of a triple-impact antioxidant, hypolipidemic, and hepatoprotective.

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“…Furthermore, methoxy-Withaferin A, although inactive for cancer cells, was shown to possess anti-stress potential in normal cells [28] suggesting side benefits of holistic extracts used in traditional home medicine that has been in practice for centuries in Ayurveda. On similar lines, we earlier identified anticancer activity in the root extract of Chinese ginseng, Helicteres angustifolia [29]. However, the active component of the extract, Cucurbitacin B (Cuc) showed cytotoxicity not only on cancer but also on normal cells [30].…”

Section: Introductionmentioning

confidence: 80%

“…Its therapeutic value has been dampened by severe toxicity in vivo [37] as shown by symptoms including diarrheal gastric upset, syncope, and respiratory failure [30]. We also previously reported its toxicity on cultured human normal fibroblasts [29].…”

Section: Discussionmentioning

confidence: 99%

Anti-Stress and Glial Differentiation Effects of a Novel Combination of Cucurbitacin B and Withanone (CucWi-N): Experimental Evidence

2018

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Background: Natural extracts and compounds used in traditional home medicine are known for their safety and a variety of health promoting and therapeutic potentials. In contrast to the single molecule mediated targets, the combinational therapies are preferred for their multi-functional and limited toxic regimens and may be useful for disease therapeutics as well as to increase the quality of life during a variety of environmental stresses. Purpose: We aimed to combine the active ingredients of Chinese (Helicteres angustifolia) and Indian (Withania somnifera) ginsengs to develop a natural, efficient, and welfare combinatorial mixture with high anti-stress and glial differentiation potentials. Methods: Using cultured cells as a model system, we developed a combination of active ingredients of Chinese (Cucurbitacin B [Cuc]) and Indian (Withanone [Wi-N]) ginsengs. Eleven chemical models of environmental stresses were used. Cytotoxicity studies were performed using human skin fibroblast for anti-stress and rat glioma cells for glial differentiation effects. Results: We demonstrate that the novel combination of Cuc and Wi-N, CucWi-N, was non-toxic to normal cells. It caused stress protection in assays using normal human fibroblasts subjected to a variety of stresses. Of note, cells showed remarkable protection against oxidative and UV stresses and marked by decrease in DNA damage and reactive oxygen species. We examined and found the glial differentiation potential of CucWi-N in rat glioblastoma cells. CucWi-N clearly induced differentiation phenotype, well-marked with upregulation of GAP43, MAP2, and GFAP, which have been shown to play a key role in glial differentiation. Conclusion: These data demonstrate anti-stress and glial differentiation potential of CucWi-N (a novel combination of Cuc and Wi-N) that could be recruited in nutraceutical and pharmaceutical avenues and hence warrant further evaluation and mechanistic studies.

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Functional Characterisation of Anticancer Activity in the Aqueous Extract of Helicteres angustifolia L. Roots

Cited by 18 publications

References 33 publications

Withaferin-A kills cancer cells with and without telomerase: chemical, computational and experimental evidences

Withaferin-A kills cancer cells with and without telomerase: chemical, computational and experimental evidences

Effects of Arctium lappa aqueous extract on lipid profile and hepatic enzyme levels of sucrose-induced metabolic syndrome in female rats

Anti-Stress and Glial Differentiation Effects of a Novel Combination of Cucurbitacin B and Withanone (CucWi-N): Experimental Evidence

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