Allicin Induces p53-Mediated Autophagy in Hep G2 Human Liver Cancer Cells

Abstract

Garlic has been used throughout history for both culinary and medicinal purpose. Allicin is a major component of crushed garlic. Although it is sensitive to heat and light and easily metabolized into various compounds such as diallyl disulfide, diallyl trisulfide, and diallyl sulfide, allicin is still a major bioactive compound of crushed garlic. The mortality of hepatocellular carcinoma is quite high and ranks among the top 10 cancer-related deaths in Taiwan. Although numerous studies have shown the cancer-preventive properties of garlic and its components, there is no study on the effect of allicin on the growth of human liver cancer cells. In this study, we focused on allicin-induced autophagic cell death in human liver cancer Hep G2 cells. Our results indicated that allicin induced p53-mediated autophagy and inhibited the viability of human hepatocellular carcinoma cell lines. Using Western blotting, we observed that allicin decreased the level of cytoplasmic p53, the PI3K/mTOR signaling pathway, and the level of Bcl-2 and increased the expression of AMPK/TSC2 and Beclin-1 signaling pathways in Hep G2 cells. In addition, the colocalization of LC3-II with MitoTracker-Red (labeling mitochondria), resulting in allicin-induced degradation of mitochondria, could be observed by confocal laser microscopy. In conclusion, allicin of garlic shows great potential as a novel chemopreventive agent for the prevention of liver cancer.

Allicin inhibits the invasion of lung adenocarcinoma cells by altering tissue inhibitor of metalloproteinase/matrix metalloproteinase balance via reducing the activity of phosphoinositide 3-kinase/AKT signaling

“…Increasing studies have demonstrated that allicin exhibits a cytotoxic effect in several human cancer cells, including glioma U87, liver cancer G2 and gastric cancer MGC803 cells (15)(16)(17). These high specificities make allicin a promising anticancer agent for lung adenocarcinoma.…”

“…Previous studies demonstrated that allicin may induce tumor cell apoptosis, inhibit the tumor cell cycle and regulate angiogenesis (14)(15)(16)(17). Numerous mechanisms are involved in the biological activities of allicin, including unfolded protein response, p53-mediated autophagy and p38 mitogen-activated protein kinase/caspase-3 signaling (14)(15)(16)(17)(18). However, to the best of our knowledge, the effects and mechanisms of allicin on lung adenocarcinoma remain undefined.…”

“…It also provided evidence that the mechanism underlying the aforementioned effects was associated with altering TIMP/MMP balance, which was regulated by the PI3K/AKT signaling pathway. The present study shed light on the investigation of allicin in lung adenocarcinoma invasion.Increasing studies have demonstrated that allicin exhibits a cytotoxic effect in several human cancer cells, including glioma U87, liver cancer G2 and gastric cancer MGC803 cells (15)(16)(17). These high specificities make allicin a promising anticancer agent for lung adenocarcinoma.…”

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

“…Bufalin, a component from toad skin, has been demon strated to induce AMPactivated protein kinase (AMPK) dependent autophagy accompanied by enhanced Beclin1 expression and LC3Ⅰ to LC3Ⅱ conversion, and decreased p62 expression and mTOR signaling in HepG2 cells [148] . Allicin, a major phytochemical of crushed garlic, is effective to induce autophagy in HepG2 cells by decreasing the level of cytoplasmic p53, the PI3K/mTOR signaling pathway, and Bcl2 and upregulating the expression of AMPK/tuberous sclerosis protein 2 and Beclin1 [149] . Shikonin, a naphthoquinone from ZiCao (Lithospermum erythrorhizon), could induce autophagy and reactive oxygen species generation which further activates ERK [150] (Figure 1).…”

Autophagy-associated Targeting Pathways of Natural Products during Cancer Treatment

“…However, garlic-induced autophagy has also reported in many studies. For example, allicin can induce p53-mediated autophagy, and inhibit the survivability of human hepatoma cells, which reveals the declined p53 expression in the cytoplasm of HepG2 cells, inhibited PI3K/mTOR signal pathway, reduced Bcl-2 expression and enhanced signal transduction pathways of AMPK/ TSC2 and Beclin 1 (Chu et al, 2012).…”