Cellular and Molecular Mechanisms of Garlic Compounds in Common GI Cancers

Abstract

The major gastrointestinal (GI) tract cancers are stomach, colorectal, pancreas, and liver cancers, which are foremost prevalent cancers worldwide, accounting for more deaths than any other cancers of human body. The GI tract cancers affect both men and women with preventable lifestyle risk factors including diet. Garlic is a globally used food ingredient with innumerable medicinal benefits due to the presence of sulfur-containing natural constituents such as alliin, methiin, DAS, DADS, DATS, SAC, and SAMC. They reduce GI cancer growth by inhibiting proliferation through disruption of microtubule-mediated cytoskeleton formation, inhibiting different cyclin/cyclin-dependent kinases in a phase-specific manner, and inducing apoptosis through mitochondrial dependent and independent pathways. The garlic compounds inhibit angiogenesis in GI cancers by downregulating VEGF, AKT/ERK, and NO signaling in tumor-induced endothelial cells. They also inhibit metastasis by inhibiting NF-κB and MMP2/9 signaling pathways. They exhibit antitumor by increasing the activity of NK cells, by secreting cytokine and chemokines, and by enhancing phagocytic activity of macrophages. Therefore, the consumption of garlic compounds may provide some kind of preventive mechanism against GI cancers through modulation of immune system.