Molecular targets of cancer chemoprevention by garlic-derived organosulfides. Acta Pharmacol Sin

Department of Molecular Biology, University of Gdañsk, Kladki 24, 80-822 Gdañsk, Poland.
Acta Pharmacologica Sinica (Impact Factor: 2.91). 10/2007; 28(9):1355-64. DOI: 10.1111/j.1745-7254.2007.00682.x
Source: PubMed


The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables including garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer cells are frequently associated with perturbations in cell cycle progression and induction of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bcl-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC.

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Available from: Anna Herman-Antosiewicz
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    • "Moreover, the anticarcinogenic effect of Allium vegetables including fresh garlic was revealed and is attributed to OSC, which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. On the other hand, anti-angiogenic activity for garlic-derived OSC has also been documented (Herman-Antosiewicz et al., 2007 ▶). "
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    ABSTRACT: Objective: The present study was hypothesized to investigate the beneficial effects of fresh, aged, and cooked garlic extracts on blood glucose and memory of diabetic rats induced by streptozocine (STZ). Material and Methods: Diabetes was induced by an intraperitoneal injection of STZ (60 mg/kg body weight). An oral dose of 1000 mg/kg of each garlic extract was given daily for 4 weeks after diabetes induction. Five days after STZ injection, five groups were formed: Control (intact) rats (Cont) + Vehicle of garlic extract (normal saline) (Veh), STZ + Veh, STZ + Fresh (row) garlic (FG), STZ + Aged garlic (AG), and STZ + cooked (boiled) garlic (CG). In order to assess the passive avoidance memory, rats were gently placed on the wooden platform, and latency to step-down (SDL) was recorded as initial phase, after then a light electrical shock [0.3 mA, 3 sec, Alternative current (AC)] was delivered to their foot paw. The retrieval tests were done for short- and long-term memories, respectively. Blood glucose was assayed by glucometer before and after treatment with STZ and garlic extracts. Results: Hyperglycemia induced by STZ decreased short-term memory in both diabetic males and females rats significantly compared with the controls (p<0.001 and p<0.01). Fresh and cooked but not aged garlic extracts decreased blood glucose in diabetic males and increased memory in both diabetic male and female rats significantly (p<0.05 and p<0.01). Conclusions: STZ causes elevation of the blood glucose and resulted in memory deficits, possibly viafree radicals production in brain tissue. Garlic has some bioactive chemicals including allicin and sulfur compound (OSC) which could lower the blood glucose during chronic hyperglycemia, inhibit free radicals production in brain, and improve short-term (but not long-term) memory.
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    • "Although an increasing amount of data indicate that DATS can suppress the growth of cultured cancer cells by causing cell cycle arrest at G2/M phase and generation of apoptosis [26-29,35-37], little is known about the effects of this compound on the growth of human leukemia cells. In the present study, we demonstrated that DATS-induced anti-proliferative effects in four leukemia cell lines (U937, THP-1, HL60 and K562) were related to induction of apoptosis, as confirmed by measurement of chromatin condensation of nuclei, DNA fragmentation, and induction of sub-G1 phase. "
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    ABSTRACT: Diallyl trisulfide (DATS) is one of the major constituents in garlic oil and has demonstrated various pharmacological activities, including antimicrobial, antihyperlipidemic, antithrombotic, and anticancer effects. However, the mechanisms of antiproliferative activity in leukemia cells are not fully understood. In this study, the apoptotic effects of DATS were investigated in human leukemia cells. Results of this study indicated that treatment with DATS resulted in significantly inhibited leukemia cell growth in a concentration- and time-dependent manner by induction of apoptosis. In U937 cells, DATS-induced apoptosis was correlated with down-regulation of Bcl-2, XIAP, and cIAP-1 protein levels, cleavage of Bid proteins, activation of caspases, and collapse of mitochondrial membrane potential. The data further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, which was attenuated by pretreatment with antioxidant N-acetyl-l-cysteine (NAC), a scavenger of ROS. In addition, administration of NAC resulted in significant inhibition of DATS-induced apoptosis by inhibiting activation of caspases. The present study reveals that the cytotoxicity caused by DATS is mediated by generation of ROS and subsequent activation of the ROS-dependent caspase pathway in U937 leukemia cells.
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    • "The risk of breast cancer was shown to decrease as consumption of alliums was increased in a French case-control study [113]. It was found that garlic and some of its constituents prevent tumor initiation by inhibiting the activation of pro-carcinogens and by stimulating their elimination [116] [117] [118]. Some studies say that onion extracts can inhibit the mutation process [119] and reduce the proliferation of cancer cells [120]. "

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