Anti-Cancer Effect of Thiacremonone through Down Regulation of Peroxiredoxin 6

Abstract

Thiacremonone (2, 4-dihydroxy-2, 5-dimethyl-thiophene-3-one) is an antioxidant substance as a novel sulfur compound generated from High-Temperature-High-Pressure-treated garlic. Peroxiredoxin 6 (PRDX6) is a member of peroxidases, and has glutathione peroxidase and calcium-independent phospholipase A2 (iPLA2) activities. Several studies have demonstrated that PRDX6 stimulates lung cancer cell growth via an increase of glutathione peroxidase activity. A docking model study and pull down assay showed that thiacremonone completely fits on the active site (cys-47) of glutathione peroxidase of PRDX6 and interacts with PRDX6. Thus, we investigated whether thiacremonone inhibits cell growth by blocking glutathione peroxidase of PRDX6 in the human lung cancer cells, A549 and NCI-H460. Thiacremonone (0–50 μg/ml) inhibited lung cancer cell growth in a concentration dependent manner through induction of apoptotic cell death accompanied by induction of cleaved caspase-3, -8, -9, Bax, p21 and p53, but decrease of xIAP, cIAP and Bcl2 expression. Thiacremonone further inhibited glutathione peroxidase activity in lung cancer cells. However, the cell growth inhibitory effect of thiacremonone was not observed in the lung cancer cells transfected with mutant PRDX6 (C47S) and in the presence of dithiothreitol and glutathione. In an allograft in vivo model, thiacremonone (30 mg/kg) also inhibited tumor growth accompanied with the reduction of PRDX6 expression and glutathione peroxidase activity, but increased expression of cleaved caspase-3, -8, -9, Bax, p21 and p53. These data indicate that thiacremonone inhibits tumor growth via inhibition of glutathione peroxidase activity of PRDX6 through interaction. These data suggest that thiacremonone may have potentially beneficial effects in lung cancer.

Roles of peroxiredoxins in cancer, neurodegenerative diseases and inflammatory diseases

“…PRDX6 promotes lung tumor development via JAK2/STAT3 pathway, its GPx and iPLA2 activities, and is involved in drug resistance of several cancer types, suggesting that PRDX6 can be a therapeutic target for cancer treatment. Our recent study suggested that thiacremonone inhibits tumor growth via inhibition of glutathione peroxidase activity of PRDX6 through interaction, suggesting that thiacremonone may have potential beneficial effects in lung cancer (Jo et al, 2014). These data indicate that PRDX6 could be targets of several cancers and the therapeutic agents for targeting PRDX6 may have potentially beneficial effects in cancer treatment.…”

Inhibitory effect of thiacremonone on MPTP-induced dopaminergic neurodegeneration through inhibition of p38 activation

“…Preparing method of thiacremonone was done as described previously [35]. This fraction containing thiacremonone was purified by preparative RP-HPLC on a Younglin SP930D Instrument [30].…”

Anticancer Herbs for Improving the Quality of Life

“…A compound extracted from the garlic, Z-ajoene is useful in the treatment of gioblastoma [25,72]. Another sulphur compound of garlic extract Thiacremonone, inhibits the lung cancer cell growth via inhibiting the Gpx activity of peroxiredoxin 6 through interaction [73]. -11, 2018 The mechanism showing the antitumor activity, stimulating the lymphocytes and macrophages used to kill cancer cells and interfaces with tumour cells metabolism is shown in figure 7.…”