• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.8
• /
• pp.3509-3515
• /
• 2015

Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). Materials and Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. Results: In $KG1{\alpha}$ cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. Conclusions: These results suggested that DADS suppressed the proliferation of $KG1{\alpha}$ cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

• Asian-Australasian Journal of Animal Sciences
• /
• v.32 no.8
• /
• pp.1205-1210
• /
• 2019

Objective: The inhibitory effects of dietary antioxidants, diallyl disulfide (DADS) and quercetin, in marinade were investigated on the formation of carcinogenic polycyclic aromatic hydrocarbons (EPA priority 16 PAHs) in grilled pork. Methods: The formation of PAHs in grilled sirloin pork with different marinades after charcoal-grilling for 2 min/side were evaluated using high performance liquid chromatography with a photodiode array detector (HPLC-DAD). Results: Compared with the control marinade treatment (without antioxidant), the addition of DADS (500 mg/kg meat sample) in marinade significantly decreased benzo[a]pyrene (BaP) (100%) and heavy PAHs (84%) in charcoal-grilled pork, while the addition of quercetin at the same concentration could reduce 23% and 55% of BaP and heavy PAHs, respectively. Conclusion: The results of this study suggested that the addition of DADS in the marinade could be important in decreasing the levels of PAHs in grilled meat.

• Biomolecules & Therapeutics
• /
• v.23 no.2
• /
• pp.180-188
• /
• 2015

This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-${\kappa}B$), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-${\kappa}B$ and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.41 no.5
• /
• pp.661-665
• /
• 2012

Garlic (Allium sativum L.) is one of the oldest cultivated plants and has been used throughout the world as a food supplement and a folk medicine for thousands of years. Raw garlic has been processed into a variety of commercial garlic products for consumer convenience. The latest new processing technology, 'spontaneous short-term fermentation', has been developed to process raw garlic into black garlic. The physiologically active effects of garlic have been attributed to its organosulfur compounds. In this study, the proximate compositions and the total amino acid content of raw Namhae garlic and black garlic were determined. The two major organosulfur compounds of garlic, $S$-allyl-L-cysteine (SAC), and diallyl-disulfide (DADS), were also analyzed using RP-HPLC. The proximate compositions were not different between raw and black garlic. The amount of 13 amino acids was greater in black garlic than in raw garlic among a total of 17 amino acids considered. The black garlic had 2-fold higher levels of SAC and 30-fold higher levels of DADS than the raw garlic. Therefore, it is suggested that consuming black garlic produced by spontaneous short-term fermentation is more effective than consuming raw garlic, in order for consumers to take more physiologically active organosulfur compounds (SAC and DADS), which are the compounds that are good for consumer health.

• Food Science and Biotechnology
• /
• v.14 no.2
• /
• pp.297-300
• /
• 2005

Effects of allyl sulfides on kinetic behavior of cytochrome P450 1 (CYP1)-catalyzed ethoxyresorufin O-deethylase (EROD) activity were studied using microsomes from benzo[a]pyrene-treated human hepatoma cells. Apparent $K_m$ and $V_{max}$ values were calculated as $2.8\;{\mu}M$ and $3.0\;{\mu}mol$ resorufin/min/mg protein based on Lineweaver-Burk plot of microsomal EROD activity, respectively. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) affected $K_m$ and $V_{max}$ values of EROD activity and acted as mixed-type inhibitors for CYP1 isozymes. Apparent Ki values of DADS and DATS were calculated as 1.07 and 0.88 mM, respectively, by re-plotting slopes of Lineweaver-Burk plot and inhibitor concentrations.

• Journal of Life Science
• /
• v.33 no.4
• /
• pp.349-356
• /
• 2023

Gout, a chronic inflammatory arthritic disease, is characterized by hyperuricemia. Gout can be induced by an inflammatory response to monosodium urate (MSU) crystals mediated by pro-inflammatory cytokine release following activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Many sulfur-containing phytochemical compounds in garlic (Allium sativum L.) are considered active ingredients because of their potential pharmacological benefits for various diseases, but their efficacy in NLRP3 inflammasome activation-mediated gout has not been demonstrated. In this study, we investigated whether diallyl disulfide (DADS) and diallyl trisulfide (DATS), representative garlic-derived sulfur compounds, have an inhibitory effect on MSU-induced NLRP3 inflammasome activation. Our results showed that under non-cytotoxic conditions, DADS and DATS significantly blocked nitric oxide production and interleukin (IL)-1β release in response to MSU in lipopolysaccharide (LPS)-primed RAW 264.7 macrophages. DADS and DATS also attenuated enhanced expression of NLRP3 and its adapter protein, apoptosis-associated speck-like protein, which was associated with downregulation of and caspase-1 p20 and IL-1β expression, suggesting that MSU-induced LRP3 inflammasome activation was counteracted by DADS and DATS. Furthermore, DADS and DATS blocked oxidative stress, an upstream event for NLRP3 inflammasome activation, as evidenced by the fact that they scavenged reactive oxygen species (ROS) production. Taken together, our findings demonstrate that DADS and DATS suppressed NLRP3 inflammasome activation by inhibiting the ROS/NLRP3 pathway and that they have potential as treatments for NLRP3-dependent gouty arthritis.