| Summary: | 碩士 === 國立臺灣大學 === 食品科技研究所 === 99 === The incidence of melanoma increased more rapidly than any other cancer in recent years. Malignancies arising in the skin are broadly divided into two categories: melanoma and non-melanoma skin cancers. Melanoma is the most serious, highly invasive and metastatic skin tumor, and even resistant to chemotherapy. Numerous studies have shown that garlic (Allium sativum L.) oil and their major active compounds - diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) exhibit the anticancer activity against several cancer types, but their effects and related mechanisms of garlic oil on human melanoma cells were not clear yet. The objective of our study was to investigate the anticancer effect of garlic essential oil on human melanoma A375 cells in vitro and in vivo assays. Garlic essential oil is obtained by steam distillation which yield accounts for 0.2–0.5%. We have evaluated the profiles of allyl sulfides in garlic oil, including DAS (5%), DADS (61%), DATS (22%) using gas chromatography.
The results indicated that garlic oil inhibited cell viability in a dose dependent manner. Flow cytometry analysis and Western blot results showed garlic oil significantly induced G2/M phase arrest of A375 cells. We further demonstrated that garlic oil elicited apoptotic events such as mitochondrial membrane depolarization, increasing intracellular reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3 and poly(ADP-ribose)polymerase (PARP). Additionally, garlic oil inhibited cell migration and invasion of A375 cells by in vitro anti-invasive assay. The activities and protein expressions of matrix metalloproteinase (MMP)-2 and -9 in A375 cells were inhibited by treatment with garlic oil. Moreover, we also showed that garlic oil suppressed anchorage-independent growth of A375 cells. The anti-proliferative potency might relate to inhibit phosphorylation of MEK/MAPK [MAPK (mitogen-activated protein kinase)/ERK (extracellular signal regulated kinase) kinase] pathway.
We also studied the anti-tumor activity of garlic oil and DATS in A375 tumor-bearing nude mice model. Garlic oil and DATS was administered for 1 week before inoculation of A375 cells and continued for 9 weeks. This results indicated that oral administration of garlic oil (117.6 mg/kg bw) and DATS (66.7 mg/kg bw) has potential to reduce tumor volume and weight as compared with negative control in xenografted nude mice; tumor volume was inhibited by 62 and 84% (p<0.05); tumor weight was inhibited by 45 and 83% (p<0.05), respectively. Furthermore, there was no significant difference in body weights among the various groups at the end of the study. The AST, ALT, BUN and creatine values showed no significant difference between treatment groups and control group. The results implied that garlic oil and DATS feeding to mice did not appear to induce any adverse effects.
In conclusion, garlic oil inhibited cell growth of human melanoma cells via induction of cell cycle arrest and apoptosis, and might provide the anti-metastatic and anti-proliferative potency. Therefore, these finding demonstrated that garlic oil and DATS exhibit anti-tumor effects in vivo model.
These results suggest that garlic oil provide the potential anticancer effect on anti-melanoma.
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