| Summary: | 碩士 === 國立臺灣大學 === 食品科技研究所 === 94 === Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are oil-soluble organosulfur compounds in processed garlic. They were well known to have chemopreventive activity against human cancer such as colon, lung, liver and skin cancer. Previous researches about the three compounds have shown that they have many biological activities, such as anti-oxidation, anti-inflammation, anti-tumor, anti-cancer, reduction of blood pressure and so on. In this study, DAS, DADS and DATS were used to investigate the anti-proliferative effects and mechanism on human basal cell carcinoma cells (BCC). Additionally, the effect of these three compounds on human lung cancer A549 cells and keratinocytes HaCaT cells was also studied. For BCC cells, the results indicated that DATS (IC50 0.85 mM) showed stronger anti-proliferative activity than DADS (IC50 1.55 mM) and DAS (IC50 >2 mM) after 48 hr treatment. For HaCaT cells, the results indicated that the IC50 values of DAS, DADS and DATS were all over 2 mM after 48 hr treatment. For A549 cells, it showed that DATS (IC50 0.01 mM) exhibited stronger anti-proliferative activity than DADS (IC50 0.05 mM) and DAS (IC50 0.12 mM) after 48 hr treatment. In addition, this study used flow cytometry analysis to evaluate the cell cycle effect of BCC, HaCaT and A549 cells treated with DAS, DADS and DATS. The results showed that DAS (0.01 mM) increased the percentage of sub-G1 phase; DADS (0.05 mM) induced cell cycle arrest in G2/M phase and DATS (0.01 mM) increased the percentage of sub-G1 phase after 48 hr treatment in A549 cells. For HaCaT cells, the three organosulfur compounds have no effect at these cell-cycle indicator. As for the results of cell cycle in BCC, sub-G1 phase increased after 48 hr treatment with DAS (2 mM), DADS (1 mM) and DATS (0.5 mM) in BCC cells. By the Western blot analysis, it suggested that DADS (1 mM) and DATS (0.5 mM) induced apoptosis in BCC cells which were triggered by the activation of caspase-3 and -9, upregulation of pro-apoptosis proteins Bad and Bax, downregulation of anti-apoptosis proteins Bcl-2 and Bcl-xL and degradation of PARP in BCC cells. In conclusion, DAS, DADS and DATS had greater effect on inhibiting BCC and A549 cells proliferation after 48 hr treatment than on HaCaT cell which means the three compounds effect normal skin cell lightly. And we suggested that DADS and DATS induced apoptosis in BCC cells through the mitochondrial pathway by the results of Western blot analysis. Therefore, these three garlic active components (DAS, DADS, and DATS) might be used to prevent the occurrence of BCC or to be the adjuvant constituents for therapy of BCC patients.
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