Effects of highly purified anthraquinoid compounds from Aloe vera on sensitive and multidrug resistant leukemia cells

Grimaudo, Stefania; Tolomeo, Manlio; Gancitano, R A; D’Alessandro, Natale; Aiello, Enrico

doi:10.3892/or.4.2.341

Cited by 15 publications

(14 citation statements)

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“…Furthermore, Nishikawa et al (1997) showed that danthrone enhanced epithelial mucosal cell replication in the large intestine, especially in the cecum of rats, and was associated with elevated prostaglandin E 2 levels that correlated with the dose of danthrone and the severity of diarrhea. Paradoxically, antitumorigenic effects are equally well documented for some anthraquinones (El-Shemy et al, 2010;Grimaudo et al, 1997;Zhao et al, 1999). A purified senna extract did not show any carcinogenic potential when administered via the drinking water at daily doses of 0, 5, 15, and 25 mg/kg bw to male and female Sprague Dawley rats for 2 years (Lydén-Sokolowski et al, 1993).…”

Section: Discussionmentioning

confidence: 95%

Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats

Boudreau

Mellick²,

Olson³

et al. 2012

Toxicological Sciences

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Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species. Based upon this observation, 2-year drinking water studies were conducted to assess the carcinogenic potential of an Aloe vera whole-leaf extract when administered to F344/N rats (48 per sex per group) at 0.5, 1, and 1.5%, and B6C3F1 mice (48 per sex per group) at 1, 2, and 3%. Compared with controls, survival was decreased in the 1.5% dose group of female rats. Treatment-related neoplasms and nonneoplastic lesions in both species were confined primarily to the large intestine. Incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and ascending and transverse colon were significantly higher than controls in male and female rats in the 1 and 1.5% dose groups. There were no neoplasms of the large intestine in mice or in the 0 or 0.5% dose groups of rats. Increased incidences of mucosa hyperplasia of the large intestine were observed in F344/N rats, and increased incidences of goblet cell hyperplasia of the large intestine occurred in B6C3F1 mice. These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats.

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Section: Discussionmentioning

confidence: 95%

Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats

Boudreau

Mellick²,

Olson³

et al. 2012

Toxicological Sciences

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“…Aloe-emodin was shown to have specific dose-dependent cytotoxic effects on non-epithelial tumors, in particular neuroblastoma cells; however, human epithelial tumors, blood-derived tumors, and normal fibroblasts were almost refractory to the aloeemodin treatments (44). In addition, of five purified anthraquinone compounds isolated from Aloe vera, only aloe-emodin produced cytotoxic effects against the multi-drug resistant human leukemia cells, although the effective dose range was in the micromolar concentration range (223). The aloin glycosides, aloesin and aloeresin, were devoid of anti-tumor cell activity, implying that only aloeemodin exerted cytotoxic responses.…”

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confidence: 97%

An Evaluation of the Biological and Toxicological Properties ofAloe Barbadensis(Miller), Aloe Vera

Boudreau

Beland

2006

Journal of Environmental Science and Health, Part C

510

349

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Aloe barbadensis (Miller), Aloe vera, has a long history of use as a topical and oral therapeutic. The plant is the source of two products, gel and latex, which are obtained from its fleshy leaves. Aloe vera products contain multiple constituents with potential biological and toxicological activities, yet the active components elude definition. Ingestion of Aloe vera is associated with diarrhea, electrolyte imbalance, kidney dysfunction, and conventional drug interactions; episodes of contact dermatitis, erythema, and phototoxicity have been reported from topical applications. This review examines the botany, physical and chemical properties, and biological activities of the Aloe vera plant.

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“…Another research group has already tried aloe emodin as a cytotoxic agent against human lung squamous cell carcinoma (Lee et al 2001). Grimaudo et al (1997) reported that aloe emodin showed some degree of cytotoxicity against erythroleukaemia cell lines, but only at a high concentration. Apoptosis is known to mediate HSC cell loss during recovery from fibrosis, and the control of this apoptosis may be a key to regulating fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Aloe Emodin‐Induced Apoptosis in t‐HSC/Cl‐6 Cells Involves a Mitochondria‐Mediated Pathway

Lian

Park

Hui-shan

et al. 2005

Basic Clin Pharma Tox

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The aim of our study was to clarify the apoptosis pathway induced by aloe emodin, an hydroxyanthraquinone present in aloe vera leaves, in rat hepatic stellate cells transformed by simian virus 40 (t-HSC/Cl-6), which retain the features of activated rat stellate cells. Apoptosis was determined by DNA fragmentation, caspase activity assay and western blotting analysis. Treatment of t-HSC/Cl-6 cells with 12.5, 25, or 50 mM aloe emodin inhibited t-HSC/Cl-6 cell viability in a dose-and time-dependent manner. The induction of apoptosis by aloe emodin was confirmed by typical DNA ladder formation and annexin v-propidium iodide flow-cytometric analysis. Aloe emodin treatment of t-HSC/Cl-6 cells caused activation of caspase-3 and caspase-9, detected with a caspase activity assay, although no change was observed in caspase-8 activity. Western blotting showed caspase-3 and caspase-9 active forms and the subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. Aloe emodin induced mitochondrial membrane depolarization. Our data also show that cytochrome c increased in the cytosol but decreased in the mitochondria in a time-dependent manner. Increased Bax and unchanged Bcl-2 levels resulted in an increased Bax/Bcl-2 ratio. Thus, our research provides evidence that aloe emodininduced apoptosis involves a mitochondria-associated apoptosis pathway.

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Effects of highly purified anthraquinoid compounds from Aloe vera on sensitive and multidrug resistant leukemia cells

Cited by 15 publications

References 0 publications

Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats

Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats

An Evaluation of the Biological and Toxicological Properties ofAloe Barbadensis(Miller), Aloe Vera

Aloe Emodin‐Induced Apoptosis in t‐HSC/Cl‐6 Cells Involves a Mitochondria‐Mediated Pathway

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