Allyl sulfides inhibit cell growth of skin cancer cells through induction of DNA damage mediated G2/M arrest and apoptosis.
Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic by steam-distillation, have been reported to provide the anticancer activity in several cancer types. However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we used human melanoma A375 cells and basal cell carcinoma cells as the models to elucidate the effects of these three allyl sulfides. Basal cell carcinoma (BCC) is known to be the most prevalent type of skin cancer, and melanoma is the most lethal form. We found that 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 (DeltaPsim). Western blot results showed the concordance for the expression of molecules involved in G(2)/M arrest and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of p53 pathway in response to the oxidative DNA damage. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Taken together, these results suggest that DATS is a potential anticancer compound for skin cancer.
Wang
Hsiao Chi
HC
Graduate Institute of Food Science and Technology, National Taiwan University, No 1, Sec 4, Roosevelt Road, Taipei 106, Taiwan.
Yang
Jen-Hung
JH
Hsieh
Shu-Chen
SC
Sheen
Lee-Yan
LY
D000498:Allyl Compounds / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D013440:Sulfides / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000498:Allyl Compounds; D017382:Reactive Oxygen Species; D013440:Sulfides; D016159:Tumor Suppressor Protein p53; C038491:allyl sulfide