Integrated genomic and proteomic studies on the molecular mechanisms of human melanoma chemoprevention by garlic essential oil and its bioactive compound （diallyl trisulfide）
Date Issued
2014
Date
2014
Author(s)
Hung, Yu-Ching
Abstract
Malignant melanoma is cancerous from melanocyte which is the most deadly kind of skin cancer. Since each melanoma cell has potential to become stem cell, it with highly invasive and metastasis characteristic, and it’s hard to cure by surgery or other cancer therapy. Some studies have found that the incidence of melanoma in western countries or Taiwan has increased year by year; therefore it is important to find the ways of prevention or adjuvant therapy to improve melanoma incidence or progression. Diallyl trisulfide (DATS), the most active component of garlic essential oil (GO), has been reported to provide antitumor activity in several cancer types. However, the actually related mechanism of GO and DATS on skin cancer is still unclear. Towards this, our lab has done the xenograft model of human melanoma in nude mice, which was established by injecting A375 cells. Tumor-induced mice were orally administered with GO (117.6 mg/kg bw) and DATS (66.7 mg/kg bw) respectively, and observed for the anti-skin tumor effects for nine weeks. The results revealed that tumor size was significantly reduced by GO and DATS treatment. The objective of this study is using genomics and proteomics technologies to investigate the molecular mechanisms of GO and DATS against human melanoma A375 cells in tumor xenograft models. Gene expression data from microarray and the differentially expressed proteins identified through 2D gel electrophoresis were integrated to elucidate the possible mechanisms of anti-tumor property. Since garlic oil analysis results are less significant, we turn to focus on DATS. Possible mechanisms of DATS against A375 induced xenograft tumor at genomics and proteomics levels revealed that DATS can reduce HMGB1 protein, cytokine IL-6, IL-1β, chemokines CCL2, CCL20 and other immune response genes and proteins expression, reducing inflammation within the tumor tissue microenvironment; DATS inhibiting glycolysis enzymes ALDOC, TPI1, PGAM1, PKM2 performance, reduce cancer cells use glycolysis to obtain energy; DATS decrease ubiquitin system-dependent enzyme protein expression, reducing tumor suppressor protein degradation-related situations; DATS inhibiting hsp27 and gelsolin apoptosis-inhibited proteins expression, and promote tumor cell death; DATS reduce metastasis-associated protein vimentin, annexin A4, gelsolin, Arp2/3, profilin 2, and ECM remodeling genes collagenI, collagen III, MMP-9 expression. In conclusion, DATS is related to inflammation by inhibiting the immune response, ubiquitination system, glycolysis path and promote apoptosis, further suppressed A375 xenograft tumor growth or metastasis. These results suggest that DATS has the potential to prevent melanoma, and can be used as secondary prevention or treatment of melanoma in the future. These results give evidences for the anti-skin tumor activity of GO’s active compound, DATS.
Subjects
皮膚癌
黑色素瘤
大蒜精油
二丙烯基三硫化物
基因體學
蛋白質體學
SDGs
Type
thesis
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