Antiproliferative effect of the garlic compound S-allyl cysteine on human neuroblastoma cells in vitro

Welch, Carrie L.; Wuarin, L.; Sidell, Neil

doi:10.1016/0304-3835(92)90263-u

Cited by 115 publications

(46 citation statements)

References 20 publications

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“…(SAC 1 ) is a significant water-soluble allyl sulfur component in garlic preparations (Weinberg et al, 1993), a component which has been shown to have antioxidant and anticancer properties in animals (Sumiyoshi and Wargovich, 1990;Hatono et al, 1996;Ho et al, 2001). SAC has been shown to have antiproliferative effects on neuroblastoma (Welch et al, 1992), melanoma (Takeyama et al, 1993), and prostate carcinoma cells (Pinto et al, 1997). However, the mechanisms of the anticancer properties of SAC are unclear.…”

Section: Introductionmentioning

confidence: 99%

Sulfoxides as Urinary Metabolites ofS-Allyl-l-Cysteine in Rats: Evidence for the Involvement of Flavin-Containing Monooxygenases

Krause¹,

Glocke²,

Elfarra³

2002

Drug Metab Dispos

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ABSTRACT:S-Allyl-L-cysteine (SAC), a component of garlic and a metabolite of allyl halides, is a known substrate for multiple flavin-containing monooxygenases (FMOs). In the current study, we characterize the in vivo SAC metabolism by investigating the presence of SAC, N-acetyl-S-allyl-L-cysteine (NASAC), and their corresponding sulfoxides in the urine of rats given SAC (200 or 400 mg/kg i.p.). In some experiments, rats were given aminooxyacetic acid (AOAA), an inhibitor of cysteine conjugate ␤-lyase, or methimazole, an alternative FMO substrate, 30 min prior to treatment with 200 mg/kg SAC. Nearly 40 to 50% of the dose was recovered in the 24-h collection period. In all treatment groups, the majority of the metabolites were excreted within 8 h. The major metabolites detected were NASAC and NASAC sulfoxide (NASACS; nearly 30-40% and 5-10% of the dose, respectively). Only small amounts of the dose (approximately 1.5%) were recovered as SAC and SAC sulfoxide (SACS). Methimazole pretreatment significantly reduced amounts of both SACS and NASACS detected in the urine when compared with rats given SAC only, whereas AOAA pretreatment had no effect. In vitro assays using rat liver microsomes were also carried out to compare the sulfoxidation rates of SAC and NASAC. The results showed that SAC was much more readily oxidized than NASAC. Collectively, the results provide evidence for the involvement of FMOs in the in vivo metabolism of SAC and that SAC is a much better substrate for FMOs than its corresponding mercapturic acid. (SAC 1 ) is a significant water-soluble allyl sulfur component in garlic preparations (Weinberg et al., 1993), a component which has been shown to have antioxidant and anticancer properties in animals (Sumiyoshi and Wargovich, 1990;Hatono et al., 1996;Ho et al., 2001). SAC has been shown to have antiproliferative effects on neuroblastoma (Welch et al., 1992), melanoma (Takeyama et al., 1993), and prostate carcinoma cells (Pinto et al., 1997). However, the mechanisms of the anticancer properties of SAC are unclear. S-Allyl-L-cysteineSAC is also a known metabolite of allyl halides and allyl esters, including allyl chloride, allyl bromide, sodium allyl sulfate, and allyl nitrate (Kaye et al., 1972;Kaye, 1973). It results from the formation of the glutathione conjugate of the allyl halide or ester. The glutamate and glycine moieties of S-allyl-glutathione are then cleaved by ␥-glutamyl transpeptidase and dipeptidases to yield SAC.Our laboratory has previously shown that SAC is a substrate for multiple rabbit and human flavin-containing monooxygenases (FMOs). FMOs are microsomal enzymes that catalyze the NADPHdependent oxidation of many compounds that contain sulfur, nitrogen, selenium, and phosphorus (Ziegler, 1993). Previously, we have shown that SAC is metabolized to the greatest extent by cDNA-expressed rabbit FMO3 followed by FMO1 and then FMO2, but SAC showed no activity with rabbit FMO5 (Ripp et al., 1997). More recently and using cDNA-expressed human FMOs, SAC has been shown to be a good substr...

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Section: Introductionmentioning

confidence: 99%

Sulfoxides as Urinary Metabolites ofS-Allyl-l-Cysteine in Rats: Evidence for the Involvement of Flavin-Containing Monooxygenases

Krause¹,

Glocke²,

Elfarra³

2002

Drug Metab Dispos

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“…S-allylcysteine (SAC), a main bioactive constituent of garlic, is an organosulfurcontaining amino acid (22). Similar to garlic extract, SAC is reported to be antioxidative (17,28), anticancer (10,39), antihepatotoxic (18,27), and can also reduce the incidence of stroke (21). In the cardiac context, Padmanabhan and Prince (29) have reported that SAC mediates cardioprotection in MI via its antioxidative properties by decreasing lipid peroxide products.…”

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confidence: 99%

S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway

Chuah¹,

Moore²,

Zhu³

2007

American Journal of Physiology-Heart and Circulatory Physiology

138

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Chuah SC, Moore PK, Zhu YZ. S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide mediated pathway. Am J Physiol Heart Circ Physiol 293: H2693-H2701, 2007. First published August 31, 2007; doi:10.1152 doi:10. /ajpheart.00853.2007 is an organosulfur-containing compound derived from garlic. Studies have shown that garlic is beneficial in the treatment of cardiovascular diseases. This study aims to elucidate if SAC is responsible for this cardioprotection using acute myocardial infarction (AMI) rat models. In addition, we hypothesized that SAC may mediate cardioprotection via a hydrogen sulfide (H2S)-related pathway. Rats were pretreated with saline, SAC (50 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), SAC ϩ propagylglycine (PAG; 50 mg ϩ 10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) or PAG (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) for 7 days before AMI induction and killed 48 h after. Our results showed that SAC significantly lowered mortality (12.5% vs. 33.3%, P Ͻ 0.05) and reduced infarct size. SAC ϩ PAG-and PAG-treated rats had larger infarct sizes than controls (60.9 Ϯ 0.01 and 62.0 Ϯ 0.03%, respectively, vs. 50.0 Ϯ 0.03%; P Ͻ 0.05). Pretreatment with SAC did not affect BP, but BP was significantly elevated in SAC ϩ PAG and PAG-treated groups (P Ͻ 0.05). In addition, plasma H2S levels and left ventricular cystathionine-␥-lyase (CSE) activities were analyzed to investigate the involvement of H2S. CSE is the enzyme responsible for H2S production in the heart. SAC increased left ventricular CSE activity in AMI rats (2.75 Ϯ 0.34 vs. 1.23 Ϯ 0.16 mol ⅐ g protein Ϫ1 ⅐ h Ϫ1 ; P Ͻ 0.01). SAC ϩ PAG-treated rats had significantly lower CSE activity compared with the SAC-treated group (1.22 Ϯ 0.27 vs. 2.75 Ϯ 0.34 mol ⅐ g protein Ϫ1 ⅐ h Ϫ1 ; P Ͻ 0.05). Similarly, SAC-treated rats had higher plasma H2S concentration compared with controls and the SAC ϩ PAG-treated group. Protein expression studies revealed that SAC upregulated CSE expression (1.1-fold of control; P Ͻ 0.05), whereas SAC ϩ PAG and PAG downregulated its expression (0.88-fold of control in both groups; P Ͻ 0.005). In conclusion, our study provides novel evidence that SAC is protective in myocardial infarction via an H2S-related pathway.

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“…마늘은 특유의 냄새와 독특한 맛으로 인하여 예로부터 향신 료와 민간약으로 널리 사용되어 왔으며 최근 들어 높은 사망 률을 나타내는 여러 종류의 암 [1,9]이나 고혈압 [8], 동맥경화 [6], 혈중지질 및 콜레스테롤 저하효과 [3,4,37], 항혈전 [18]의 예 방과 치료에 효능이 있다고 알려지면서 많은 연구가 진행되고 있다. 마늘의 유효성분인 allicin은 마늘 특유의 휘발성 향기 성분으로 마늘조직이 파괴될 때 allinase에 의하여 생성되며 allicin이 분해되면 diallyl sulfide, diallyl disulfide, dithiin, ajoene 등의 휘발성 성분과 S-allylcysteine (SAC), S-allylmercaptocysteine 등의 수용성 유황화합물로 분해되어 효능을 나 타낸다 [23].…”

Section: 서 론unclassified

Effects of Aged Black Garlic Extract on Lipid Improvement in Rats Fed with High Fat-Cholesterol Diet

이현숙¹,

양승택²,

류병호³

2011

Journal of Life Science

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This study was performed to investigate the increase of S-allylcysteine content, a biomarker of black garlic, during its aging period, as well as the serum lipid-lowering effects of black garlic extract in high fat diet fed rats. The highest content of S-allylcysteine was observed on the 15th day of the aging period. Sensory evaluation was also estimated to be extremely good on the 15th day of the aging period. High fat diet rats with induced hyperlipidemia were fed diets containing black garlic extract of low, medium, and high doses for 6 weeks. No significant difference in body weight gain and food efficiency was observed between normal, placebo and black garlic fed groups. Liver weight was significantly higher in black garlic fed groups than in the normal group. Total serum cholesterol and triglyceride were significantly lower in low, medium, and high dose groups than in the normal group. Also, HDL-cholesterol was significantly higher and LDL-cholesterol was significantly lower in black garlic diet fed groups than in the normal group. Hepatic levels including total lipid and cholesterol were especially decreased in the black garlic diet fed group than in the placebo group. These results suggest that black garlic intake reduces the levels of serum and hepatic cholesterol in high fat diet fed rats. In conclusion, black garlic has a potential to be used as a functional health food ingredient with beneficial effects on lowering cholesterol and triglyceride levels.

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Antiproliferative effect of the garlic compound S-allyl cysteine on human neuroblastoma cells in vitro

Cited by 115 publications

References 20 publications

Sulfoxides as Urinary Metabolites ofS-Allyl-l-Cysteine in Rats: Evidence for the Involvement of Flavin-Containing Monooxygenases

Sulfoxides as Urinary Metabolites ofS-Allyl-l-Cysteine in Rats: Evidence for the Involvement of Flavin-Containing Monooxygenases

S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway

Effects of Aged Black Garlic Extract on Lipid Improvement in Rats Fed with High Fat-Cholesterol Diet

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