Prooxidant activity of curcumin: copper-dependent formation of 8-hydroxy-2'-deoxyguanosine in DNA and induction of apoptotic cell death.
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.
Yoshino
Masataka
M
Department of Biochemistry, School of Medicine, Aichi Medical University, Yazako, Nagakute, Aichi 480-1195, Japan. yoshino@aichi-med-u.ac.jp
Haneda
Miyako
M
Naruse
Makoto
M
Htay
Hla Hla
HH
Tsubouchi
Ryoko
R
Qiao
Shan Lou
SL
Li
Wei Hua
WH
Murakami
Keiko
K
Yokochi
Takashi
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D003300:Copper / Q000633:toxicity*; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D017665:Hydroxyl Radical / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D017382:Reactive Oxygen Species; D013950:Thymus Gland
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016877:Oxidants; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D003300:Copper; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D003474:Curcumin