Jeong Yun-Mi, Lee Ju Eun, Kim Su Yeon, Yun Hye-Young, Baek Kwang Jin, Kwon Nyoun Soo, Kim Dong-Seok
Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Korea.
Pharmazie. 2009 Dec;64(12):829-33.
Ultraviolet (UV) radiation is a major risk factor for the development of melanoma. Recent studies have reported that the intake of citrate-containing juices may reduce the risk of cancer. Thus, we investigated the effects of citrate on UVB-irradiated B16 murine melanoma cells. B16 cells had more evident apoptotic features with the combination of citrate/UVB than by citrate or UVB alone; cell death of HaCaT human keratinocytes was not observed with citrate/UVB. Western blot analysis demonstrated that citrate/UVB led to phosphorylation of the stress signaling proteins, such as c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Furthermore, citrate/UVB caused activation of caspase-9/-3 as well as cleavage of poly(ADP-ribose) polymerase (PARP). Correspondingly, cell cycle analysis showed that citrate/UVB clearly increased the sub-G0/G1 phase, which indicated apoptotic cell death of B16 cells. Therefore, our study has demonstrated that sub-lethal doses of citrate enhanced the apoptotic cell death of melanoma cells under UVB irradiation. From these results, we suggest that citrate might reduce the risk of developing melanoma induced by UVB.
紫外线（UV）辐射是黑色素瘤发生的主要风险因素。最近的研究报告称，摄入含柠檬酸盐的果汁可能会降低患癌风险。因此，我们研究了柠檬酸盐对紫外线B（UVB）照射的B16小鼠黑色素瘤细胞的影响。与单独使用柠檬酸盐或UVB相比，柠檬酸盐/UVB联合处理时B16细胞具有更明显的凋亡特征；柠檬酸盐/UVB处理未观察到HaCaT人角质形成细胞的细胞死亡。蛋白质免疫印迹分析表明，柠檬酸盐/UVB导致应激信号蛋白磷酸化，如c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPK）。此外，柠檬酸盐/UVB引起半胱天冬酶-9/-3的激活以及聚（ADP-核糖）聚合酶（PARP）的裂解。相应地，细胞周期分析表明，柠檬酸盐/UVB明显增加了亚G0/G1期，这表明B16细胞发生凋亡性细胞死亡。因此，我们的研究表明，亚致死剂量的柠檬酸盐可增强UVB照射下黑色素瘤细胞的凋亡性细胞死亡。基于这些结果，我们认为柠檬酸盐可能会降低UVB诱导的黑色素瘤发生风险。
