Prooxidant activity of curcumin: copper-dependent formation of 8-hydroxy-2 ′-deoxyguanosine in DNA and induction of apoptotic cell death

• Published in: Toxicology in vitro 2004-12, Vol.18 (6), p.783-789
• Main Authors: Yoshino, Masataka, Haneda, Miyako, Naruse, Makoto, Htay, Hla Hla, Tsubouchi, Ryoko, Qiao, Shan Lou, Li, Wei Hua, Murakami, Keiko, Yokochi, Takashi
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2 ′-deoxyguanosine; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Apoptosis; Apoptosis - drug effects; Cattle; Copper - toxicity; Curcumin; Curcumin - pharmacology; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - analysis; Deoxyguanosine - chemistry; DNA Damage; Flow Cytometry; HL-60 Cells; Humans; Hydroxyl radical; Hydroxyl Radical - pharmacology; Oxidants - pharmacology; Plasmids - genetics; Reactive Oxygen Species; Thymus Gland
• ISSN: 0887-2333; 1879-3177
• 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 β-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 β-diketone structure of this compound.