In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma

Devi, P. Uma; Sharada, A.C.; Solomon, F. Emerson

doi:10.1016/0304-3835(95)03892-z

Cited by 64 publications

(33 citation statements)

References 4 publications

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“…WA has been shown to exert antitumor properties (Devi et al, 1995;Sharada et al, 1996). However, the involved direct molecular target has never been identified.…”

Section: Discussionmentioning

confidence: 99%

“…So far, more than 35 chemical constituents have been isolated from this plant, including alkaloids and withanolides, of which Withaferin A (WA), a steroidal lactone, is the most important (Mishra et al, 2000). Several properties of WA have been reported: antitumor effect, radiosensitizing activity (Devi et al, 1995(Devi et al, , 2000Sharada et al, 1996;Devi and Kamath, 2003), antiangiogenesis through NF-B inhibition (Mohan et al, 2004;Yokota et al, 2006), cytoskeletal architecture alteration by covalently binding annexin II (Falsey et al, 2006), and apoptosis induction through the protein kinase C pathway in leishmanial cells (Sen et al, 2007).…”

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confidence: 99%

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The Tumor Proteasome Is a Primary Target for the Natural Anticancer Compound Withaferin A Isolated from “Indian Winter Cherry”

Yang¹,

Shi²,

Dou³

2006

Mol Pharmacol

197

168

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Withaferin A (WA) is a steroidal lactone purified from medicinal plant "Indian Winter Cherry" that is widely researched for its variety of properties, including antitumor effects. However, the primary molecular target of WA is unknown. By chemical structure analysis, we hypothesized that Withaferin A might be a natural proteasome inhibitor. Computational modeling studies consistently predict that C 1 and C 24 of WA are highly susceptible toward a nucleophilic attack by the hydroxyl group of N-terminal threonine of the proteasomal chymotrypsin subunit ␤5. Furthermore, WA potently inhibits the chymotrypsin-like activity of a purified rabbit 20S proteasome (IC 50 ϭ 4.5 M) and 26S proteasome in human prostate cancer cultures (at 5-10 M) and xenografts (4 -8 mg/kg/day). Inhibition of prostate tumor cellular proteasome activity in cultures and in vivo by WA results in accumulation of ubiquitinated proteins and three proteasome target proteins (Bax, p27, and IB-␣) accompanied by androgen receptor protein suppression (in androgen-dependent LNCaP cells) and apoptosis induction. Treatment of WA under conditions of the aromatic ketone reduction, or reduced form of Celastrol, had significantly decreased the proteasomeinhibitory and apoptosis-inducing activities. Treatment of human prostate PC-3 xenografts with WA for 24 days resulted in 70% inhibition of tumor growth in nude mice, associated with 56% inhibition of the tumor tissue proteasomal chymotrypsinlike activity. Our results demonstrate that the tumor proteasome ␤5 subunit is the primary target of WA, and inhibition of the proteasomal chymotrypsin-like activity by WA in vivo is responsible for, or contributes to, the antitumor effect of this ancient medicinal compound.

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“…WA has been shown to exert antitumor properties (Devi et al, 1995;Sharada et al, 1996). However, the involved direct molecular target has never been identified.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Tumor Proteasome Is a Primary Target for the Natural Anticancer Compound Withaferin A Isolated from “Indian Winter Cherry”

Yang¹,

Shi²,

Dou³

2006

Mol Pharmacol

197

168

View full text Add to dashboard Cite

show abstract

“…Similarly, phytochemicals like withaferin and plumbagin, isolated from Withania somnifera and Plumbago rosea have been reported to enhance the antitumor effect of radiation in EAC bearing mice. [47][48][49][50] The optimum dose of 50 mg/kg body wt APE in conjunction with 6 Gy irradiation has been found to be most effective while the other higher doses of APE did not enhance the radiation effect further. This effect may be attributed to the elevation of radiation-induced free radicals by APE.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Radiation Effect by <i>Aphanamixis polystachya</i> in Mice Transplanted with Ehrlich Ascites Carcinoma

Jagetia

Venkatesha

2005

Biological & Pharmaceutical Bulletin

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The effect of radiation on tumor tissue can be optimized by adding radiosensitizing agents, in order to achieve a greater degree of tumor damage than expected from the use of either treatment alone. The ethanolic extract of Aphanamixis polystachya (APE) was tested in Swiss albino mice transplanted with Ehrlich ascites carcinoma (EAC) and exposed to various doses of g g-radiation. EAC mice received 0, 10, 25, 50, 75, 100, 150 or 200 mg/kg body wt APE before exposure to 6 Gy g g-radiation followed by once daily administration for another 8 consecutive days post-irradiation. The optimum radiosensitizing dose was found to be 50 mg/kg APE that was further tested in EAC mice exposed to 0, 1, 2, 4, 6 or 8 Gy hemi body g g-radiation. The best effect of APE and radiation was observed for 6 Gy g g-radiation. The splitting of 50 mg into two equal fractions of 25 mg and administering the split dose with a gap of 8 h on 1, 3, 5, 7 or 9 d of tumor inoculation resulted in an increased survival even when the drug was administered at late stages (day 5) of tumor development. The APE treatment before irradiation elevated lipid peroxidation followed by a reduction in the glutathione contents. Treatment of tumor bearing mice with APE before irradiation further reduced the activities of various antioxidant enzymes like glutathione peroxidase, glutathione-s-transferase, superoxide dismutase and catalase at different post last drug administration (PLDA) times.

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“…In this line of research, various plant products and their derivatives have been screened for their biological activities including anticancer properties [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. We have reported the chemical constituents and fatty acid profile of chia seed oil (CSO).…”

Section: Introductionmentioning

confidence: 99%

In Vitro Anticancer and Anti-Lipoxygenase Activities of Chia Seed Oil and Its Blends With Selected Vegetable Oils

Gazem

Puneeth

Madhu

et al. 2017

Asian J Pharm Clin Res

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Objective: To investigate the anticancer and anti-inflammatory potential of chia seed oil (CSO) and its blends in vitro. Methods:The in vitro cancer cytotoxic properties ability of CSO and its blends was evaluated by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) and trypan blue assays using major cell lines including chronic myelogenous leukemia, HeLa and MCF-7 cells. The anti-inflammatory effect of the CSO and its blends was studied by assessing the anti-lipoxygenase (LOX) activity in vitro.Results: Incubation with CSO alone significantly inhibited the LOX activity. In the combination groups, CSO slightly increased the inhibition among blends of soybean and palmolein oils. In addition, CSO alone and in blends demonstrated potent and differential anticancer activity in MTT and trypan blue assays. Conclusion:Our results pave the way for the conclusion that CSO alone or in combination with the vegetable oils proves to be a healthy synergistic supplement or an adjuvant for the current diet. The supplementation with CSO is suggested for the modern lifestyle to delay or prevent the incidence of degenerative disorders.

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In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma

Cited by 64 publications

References 4 publications

The Tumor Proteasome Is a Primary Target for the Natural Anticancer Compound Withaferin A Isolated from “Indian Winter Cherry”

The Tumor Proteasome Is a Primary Target for the Natural Anticancer Compound Withaferin A Isolated from “Indian Winter Cherry”

Enhancement of Radiation Effect by <i>Aphanamixis polystachya</i> in Mice Transplanted with Ehrlich Ascites Carcinoma

In Vitro Anticancer and Anti-Lipoxygenase Activities of Chia Seed Oil and Its Blends With Selected Vegetable Oils

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