隨著疾病預防與營養輔助治療觀念被重視，利用天然物預防癌症或作為輔助癌症治療，被視為可行的方法。黑色素瘤侵襲性高，且具有治療困難與造成患者高死亡率的特性。啤酒酵母富含多種營養素，並且對多種癌細胞具有細胞毒性作用，但對黑色素瘤的影響從未被研究過。因此本研究目的為探討啤酒酵母萃取物對黑色素瘤的影響。細胞實驗中，首先探討啤酒酵母萃取物對黑色素瘤細胞(B16F10)與肝上皮細胞(clone 9)的影響，以細胞存活率、細胞增殖率、細胞死亡、細胞凋亡、內質網壓力與氧化性壓力表現作為分析指標，另外，以細胞存活率分析啤酒酵母萃取物對化療藥順鉑在細胞毒性的影響。動物實驗，以腹腔注射方式給予小鼠啤酒酵母萃取物，分析腫瘤大小重量、體重變化、肝腎血清生化值與血球計數。結果顯示，啤酒酵母萃取物降低B16F10細胞存活率，但對clone 9細胞存活率無顯著影響。雖然B16F10細胞增殖率未受抑制，但細胞死亡數量、凋亡數量、凋亡相關蛋白cleaved PARP、cleaved caspase 3、caspase 9、Bax/Bcl-2比值與細胞質中細胞色素c表現量顯著增加。此外，氧化性壓力及內質網壓力相關蛋白p-eif2α與chop的表現顯著上升。啤酒酵母萃取物增加順鉑對黑色素瘤細胞存活率的抑制。動物實驗上，給予高濃度啤酒酵母萃取物組別的黑色素瘤大小與重量低於未給予啤酒酵母萃取物組，並且小鼠體重、肝腎功能指標及各類血球計數，在給予啤酒酵母萃取物後與未給予啤酒酵母萃取物組之間無顯著差異。綜合以上實驗結果，啤酒酵母萃取物通過活化氧化性壓力與內質網壓力相關的細胞凋亡途徑，抑制黑色素瘤細胞存活率，並且啤酒酵母萃取物具增加順鉑對黑色素瘤細胞毒性與抑制小鼠黑色素瘤生長，但不會對小鼠肝腎與造血功能有不良影響。

With the rise of cancer chemoprevention and nutritional support, it is feasible to prevent cancer or proceed cancer adjuvant therapy by diet. Malignant melanoma is invasive skin cancer, which can cause high mortality. Saccharomyces cerevisiae is rich in nutrients, and although studies indicate that S. cerevisiae shows cytotoxic effects on various cancer cells, its effect on melanoma has never been investigated. The aim of this study was to investigate the effects of S. cerevisiae extract on melanoma. In vitro, the parameters of cell viability, proliferation, cell death, apoptosis, endoplasmic reticulum stress (ER stress), and oxidative stress were analyzed. In vivo, the tumor size, body weight, liver and kidney biochemistry and blood cell count were analyzed. S. cerevisiae extract reduced the cell viability and increased the cell death in melanoma cells, but cell proliferation unaffected. The expression of apoptosis-related proteins, ER stress-related proteins and oxidative stress were increased. Besides, S. cerevisiae increased the inhibition of cisplatin on melanoma cell viability. In animal study, tumor size and weight in S. cerevisiae extract treated group were lower than those in untreated group. Moreover, body weight, blood cell and serum biochemical level were unaffected. In conclusion, S. cerevisiae extract inhibits the melanoma cell viability by activating oxidative stress/ER stress-associated apoptosis pathway. Furthermore, S. cerevisiae extract inhibits melanoma growth of mice and increases the toxicity of cisplatin to melanoma, and it does not have an adverse effect on hepatic, renal and hematopoietic function in mice.

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