Diallyl trisulfide selectively causes Bax‐ and Bak‐mediated apoptosis in human lung cancer cells

Abstract

Garlic-derived organosulfur compounds (OSCs) are highly effective in affording protection against chemically-induced pulmonary carcinogenesis in animal models. We now demonstrate that garlic constituent diallyl trisulfide (DATS) suppresses viability of cultured human lung cancer cell lines H358 (a non-small cell lung cancer cell line) and H460 (a large cell lung cancer cell line) by causing G2-M phase cell cycle arrest and apoptotic cell death. On the other hand, a normal human bronchial epithelial cell line BEAS-2B was significantly more resistant to growth inhibition and apoptosis induction by DATS compared with lung cancer cells. We also found that even a subtle change in the OSC structure could have a significant impact on its biological activity. For example, DATS was significantly more effective than either diallyl sulfide or diallyl disulfide against proliferation of lung cancer cells. The DATS-mediated G2-M phase cell cycle arrest was explained by down-regulation of cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C protein expression leading to accumulation of Tyr15 phosphorylated (inactive) Cdk1. The DATS-induced apoptosis correlated with induction of proapoptotic proteins Bax, Bak, and BID, and a decrease in the expression of antiapoptotic proteins Bcl-2 and Bcl-xL in lung cancer cells but not in BEAS-2B. Knockdown of Bax and Bak proteins conferred significant protection against DATS-induced apoptotic cytoplasmic histone-associated DNA fragmentation. On the other hand, BID protein was dispensable for DATSinduced apoptosis. In conclusion, the present study indicates that Bax and Bak proteins are critical targets of DATS-induced apoptosis in human lung cancer cells.

Antiproliferative effect of natural tetrasulfides in human breast cancer cells is mediated through the inhibition of the cell division cycle 25 phosphatases

“…Indeed, results obtained by Xiao et al indicated that DAS 3 -treated prostate cancer cells exhibited a decrease in Cdc25 C protein level and an increase in its Ser216 phosphorylation, creating a binding site for 14-3-3 cytoplasmic protein (7). More recently, they have reported that the DAS 3 -mediated G 2 -M cell cycle arrest was associated with a down-regulation of Cdc25 C expression (26). The latter study also shows that the induction of proapoptotic proteins and the decrease of anti-apoptotic proteins seem to be crucial in apoptosis induction.…”

Epigenetic Impact of Bioactive Dietary Compounds in Cancer Chemoprevention

“…It has been shown that diallyl trisulfide is considerably more effective than either diallyl sulfide or diallyl disulfide against lung cancer cells proliferation (Xiao et al 2009), indicating that a subtle change in the structure of these bioactive agents could have a significant impact on its biological activity.…”

“…Diallyl trisulfide, another garlic-derived organosulfur compounds, suppresses viability of human lung cancer cell lines H358 (a non-small cell lung cancer cell line) and H460 (a large cell lung cancer cell line) by causing cell cycle arrest and apoptosis (Xiao et al 2009). It has been shown that diallyl trisulfide is considerably more effective than either diallyl sulfide or diallyl disulfide against lung cancer cells proliferation (Xiao et al 2009), indicating that a subtle change in the structure of these bioactive agents could have a significant impact on its biological activity.…”

Naturally Occurring Organic Sulfur Compounds: An Example of a Multitasking Class of Phytochemicals in Anti-Cancer Research

“…OSCs activate Bax and Bak (Cerella et al, 2009;Kim, Y.A. et al, 2007;Xiao et al, 2006a;Xiao et al, 2009a). Interestingly, time-course analyses have evidenced that Bak might be activated before Bax (Cerella et al, 2009).…”