Yoshino Masataka, Haneda Miyako, Naruse Makoto, Htay Hla Hla, Tsubouchi Ryoko, Qiao Shan Lou, Li Wei Hua, Murakami Keiko, Yokochi Takashi
Department of Biochemistry, School of Medicine, Aichi Medical University, Yazako, Nagakute, Aichi 480-1195, Japan.
Toxicol In Vitro. 2004 Dec;18(6):783-9. doi: 10.1016/j.tiv.2004.03.009.
Curcumin, a well-known antioxidant in a principal ingredient of turmeric, acted as a prooxidant causing a copper-dependent DNA damage and the induction of apoptosis. Treatment of DNA from plasmid pBR322 and calf thymus with curcumin plus copper ion caused strand scission and the formation of 8-hydroxy-2(')-deoxyguanosine in DNA. Addition of catalase protected DNA from the curcumin-dependent injuries, indicating that hydroxyl radical may participate in the DNA damage. Flow cytometry analysis showed that curcumin caused an apoptotic cell death of HL60 cells in a dose- and time-dependent manner. Curcumin-mediated apoptosis was closely related to the increase in intracellular reactive oxygen species. On the contrary, capsaicinoids, which have a ortho-methoxy phenolic structure without beta-diketone in the side chain, did not produce 8-hydroxy-2(')-deoxyguanosine. Capsaicin further did not induce apoptosis of HL60 cells, but rather protected cells from prooxidant-induced apoptosis. Curcumin can generate reactive oxygen species as a prooxidant in the presence of transition metals in cells, resulting in DNA injuries and apoptotic cell death. The prooxidant action of curcumin may be related to the conjugated beta-diketone structure of this compound.
姜黄素是姜黄主要成分中一种著名的抗氧化剂，却表现为促氧化剂，导致铜依赖性DNA损伤并诱导细胞凋亡。用姜黄素加铜离子处理质粒pBR322和小牛胸腺的DNA，会导致链断裂并在DNA中形成8-羟基-2'-脱氧鸟苷。添加过氧化氢酶可保护DNA免受姜黄素依赖性损伤，表明羟基自由基可能参与了DNA损伤。流式细胞术分析表明，姜黄素以剂量和时间依赖性方式导致HL60细胞凋亡性死亡。姜黄素介导的细胞凋亡与细胞内活性氧的增加密切相关。相反，具有邻甲氧基酚结构且侧链无β-二酮的辣椒素类物质不会产生8-羟基-2'-脱氧鸟苷。辣椒素进一步不会诱导HL60细胞凋亡，反而能保护细胞免受促氧化剂诱导的凋亡。在细胞中存在过渡金属的情况下，姜黄素可作为促氧化剂产生活性氧，导致DNA损伤和凋亡性细胞死亡。姜黄素的促氧化作用可能与其共轭β-二酮结构有关。
