Anticancer activity and its molecular mechanisms of allyl sulfides of garlic essential oil in human skin cancer cells
Date Issued
2010
Date
2010
Author(s)
Wang, Hsiao-Chi
Abstract
Global incidence rate of skin cancer is rapidly increased in recent years, including basal cell carcinoma (BCC) which is the most common type of skin cancer, and malignant melanoma is most metastatic tumor. Numerous studies have shown that diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), the active components of garlic essential oil, provide the anticancer activity in several cancer types, but their effects and related mechanisms of these allyl sulfides on skin cancer are unclear. The objective of this study was to investigate the anticancer activity and its molecular mechanisms of DAS, DADS, and DATS in human melanoma A375 cells and basal cell carcinoma BCC cells. We found that allyl sulfides decreased the cell viability of skin cancer cells, and DATS revealed better growth inhibition of A375 and BCC cells than DADS and DAS did. We further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, induced cytosolic Ca(2+) mobilization, and decreased mitochondrial membrane potential. However, N-acetyl cysteine (NAC) attenuated the growth inhibition of A375 and BCC cells induced by DATS. Flow cytometry analysis and Western blot results showed the concordance for the expression of molecules involved in p53 pathway in response to DNA damage, G2/M arrest, ER stress, and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of Caspase-dependent and independent mitochondrial apoptosis pathway. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Additionally, DATS inhibited cell migration, adhesion, and invasion of A375 cells by in vitro anti-metastatic assay. The anti-metastatic potency might relate to the regulation of Integrin and focal adhesion kinase (FAK), and the decrease in the activity of matrix metalloproteinases (MMPs) induced by DATS, including MMP-2 and MMP-9. In conclusion, DATS inhibited cell growth of human skin cancer cells cells via induction of cell cycle arrest and apoptosis, and might provid the anti-metastatic potency. These results suggest that DATS is a potential anticancer compound for skin cancer.
Subjects
skin cancer
melanoma
garlic
allyl sulfides
apoptosis
oxidative stress
metastasis
SDGs
Type
thesis
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