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Growth inhibition of human tumor cell lines by withanolides from Withania somnifera leaves. Life Sci

Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.
Life Sciences (Impact Factor: 2.7). 11/2003; 74(1):125-32. DOI: 10.1016/j.lfs.2003.07.007
Source: PubMed

ABSTRACT

Ayurvedic medicines prepared in India consist of Withania somnifera roots as one of the main ingredients. It is consumed as a dietary supplement around the world. The leaves of W. somnifera were used in the treatment of tumors and inflammation in several Asian countries. We have isolated twelve withanolides such as withaferin A (1), sitoindoside IX (2), 4-(1-hydroxy-2, 2-dimethylcyclpropanone)-2, 3-dihydrowithaferin A (3), 2, 3-dihydrowithaferin A (4), 24, 25-dihydro-27-desoxywithaferin A (5), physagulin D (1-->6)-beta-D-glucopyranosyl- (1-->4)-beta-D-glucopyranoside (6), 27-O-beta-D-glucopyranosylphysagulin D (7), physagulin D (8), withanoside IV (9), and 27-O-beta-D-glucopyranosylviscosalactone B (10), 4, 16-dihydroxy-5beta, 6beta-epoxyphysagulin D (11), viscosalactone B (12) from the leaves of this species. Compounds 1-12 and diacetylwithaferin A (13) were tested for their antiproliferative activity on NCI-H460 (Lung), HCT-116 (Colon), SF-268 (Central Nervous System; CNS and MCF-7 (Breast) human tumor cell lines. The inhibitory concentration to afford 50% cell viability (IC50) for these compounds was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Withaferin A and its derivatives exhibited inhibitory concentrations (50%) ranging from 0.24 +/- 0.01 to 11.6 +/- 1.9 microg/mL. Viscosalactone B (12) showed the 50% inhibition at concentrations ranging from 0.32 +/- 0.05 to 0.47 +/- 0.15 microg/mL whereas its 27-O-glucoside derivative (10) exhibited IC50 between 7.9 +/- 2.9 and 17.3 +/- 3.9 microg/ml. However, Physagulin D type withanolides showed either weak or no activity at 30 microg/mL. Therefore, incorporation of withanolides in the diet may prevent or decrease the growth of tumors in human.

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    • "Withania somniferaor Ashwagandha, a notable medicinal herb in Solanaceae family consists of various therapeutic properties predominantly with anti-diabetic and anti-cancer properties (Udayakumar et al., 2009; Singh et al., 2010; Jayaprakasam et al., 2003). Among the vital secondary metabolites in withinia, the compound withaferin A attributes to the maximum diseases curative effect of the extract (Ray & Jha, 2001). "
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    ABSTRACT: Medicinal plants are the major source of drugs with novel therapeutic values and lesser side effects. The cultivation of medicinal plants in hydroponic system under controlled environment affords the production of plants with improved economic qualities. Especially, the incorporation of different types of spectral qualities during hydroponic cultivation aids in the enhancement of pharmaceutically valuable secondary metabolites. Among several environmental cues, light determines the vital physiological process of plants such as photosynthesis, primary and secondary metabolism. Most of the medicinal compounds isolated from the plants are synthesized as secondary metabolites via phenylpropanoid or terpenoid pathway. In general, light quality triggers the expression of genes involved in these pathways and induces the synthesis of secondary metabolites with medicinal uses. Moreover, the light quality mediated elicitation of phytochemicals with disease alleviating property in medicinal plants has been reported by several researchers. Therefore, in the current chapter the spectral quality mediated molecular regulation of secondary metabolites synthesis in medicinal plants grown under controlled environment is discussed.
    No preview · Chapter · Feb 2016
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    • "In addition to WFA, other withanolides display anticancer activity. For example, Jayaprakasam et al. [25] showed that WFA and 12 other withanolides isolated from W. somnifera display strong anticancer activity against breast, colon and lung cancer cell lines. 3-Azidowithaferin A (AzWA) inhibited cell motility and invasion and enhanced the secretion of extracellular Par-4 that abolished secretory matrix metalloproteinase 2 in human cervical and prostate cancer cells [26]. "
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    ABSTRACT: Plant-based Ayurvedic medicine has been practiced in India for thousands of years for the treatment of a variety of disorders. They are rich sources of bioactive compounds potentially useful for prevention and treatment of cancer. Withania somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is a widely used medicinal plant whose anticancer value was recognized after isolation of steroidal compounds withanolides from the leaves of this shrub. Withaferin A is the first member of withanolides to be isolated, and it is the most abundant withanolide present in W. somnifera. Its cancer-protective role has now been established using chemically induced and oncogene-driven rodent cancer models. The present review summarizes the key preclinical studies demonstrating anticancer effects of withaferin along with its molecular targets and mechanisms related to its anticancer effects. Anticancer potential of other withanolides is also discussed.
    Full-text · Article · Aug 2015
    • "These alkaloids include anaferine, anahygrine, cuscohygrine, and many others including isopelletierine along with some withanolides and withaferins such as steroidal lactones. Similarly, 12 withanolides were isolated by Jayaprakasam et al. (2003) from the leaves of W. somnifera, some of them are listed here such as 25-dihydro-27-desoxywithaferin A, physagulin D, withanoside IV, viscosalactone B (12), withaferin A, sitoindoside IX, 4-(1-hydroxy-2,2 dimethylcyclpropanone)-2,3-dihydro- withaferin A, 2,3-dihydrowithaferin A, 24-physagulin D (1–46)-b-D-glucopyranosyl-(1–44)-b-D-glucopyranoside, 27-O-b-D-glucopyranosylphysagulin D, 27-O-b-D-glucopyra- nosylviscosalactone B, and 4,16-dihydroxy-5b,6b-epoxyphy- sagulin D. Regardless of this, many researchers are engaged in isolating and evaluating the activity of chemical compounds from whole plant body of W. somnifera. Withasomniferin-A and 5-dehydroxy withanolide-R extracted from aerial plant parts were studied by Bhattacharya et al. (1987) for their immunomodulatory actions. "
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    ABSTRACT: Cancer, being a cause of death for major fraction of population worldwide, is one of the most studied diseases and is being investigated for the development of new technologies and more accurate therapies. Still the currently available therapies for cancer have many lacunae which affect the patient's health severely in the form of side effects. The natural drugs obtained from the medicinal plants provide a better alternative to fight against this devastating disease. Withania somnifera L. Dunal (Solanaceae), a well-known Ayurvedic medicinal plant, has been traditionally used to cure various ailments for centuries. Considering the immense potential of W. somnifera, this review provides a detail account of its vital phytoconstituents and summarizes the present status of the research carried out on its anticancerous activities, giving future directions. The sources of scientific literature were accessed from various electronic databases such as PubMed, Google Scholar, Science Direct, and library search. Various parts of W. somnifera especially the roots with its unique contents have been proved effective against different kinds of cancers. The most active components withanolides and withaferins along with a few other metabolites including withanone (WN) and withanosides have been reported effective against different types of cancer cell lines. This herb holds an important place among various anticancer medicinal plants. It is very essential to further screen and to investigate different formulations for anticancer therapy in vitro as well as in vivo in combination with established chemotherapy.
    No preview · Article · Apr 2015 · Pharmaceutical Biology
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