Cellular toxicity of catechin analogues containing gallate in opossum kidney proximal tubular (OK) cells.
A variety of catechins exist in green tea and Chinese rhubarb. It is also known that the green tea tannin mixture and its individual tannin components such as (-)-epicatechin 3-O-gallate (ECG) and (-)-epigallocatechin 3-O-gallate (EGCG) suppress renal failure in animals and inhibit the growth of mesangial cells. In addition, gallic acid (GA), a structural constituent of these catechins, induces apoptosis in tumor cell lines. However, the effects of catechins on renal tubular cells have not been investigated. In this experiment, the growth of opossum kidney proximal tubular (OK) cells was inhibited by GA (36.9 +/- 9.5%, p < 0.01) and EGCG (48.6 +/- 16.7%, p < 0.01) at 50 microM, and was almost completely inhibited by these compounds at concentrations over 100 microM. Furthermore, ECG inhibited the growth of OK cells at concentrations over 200 microM (52.6 +/- 16.5%, p < 0.01). The numbers of in situ end-labeled (ISEL) cells in cultures treated with GA at 25 and 50 microM, ECG at 100 and 200 microM, or EGCG at 25 microM were significantly less than those in the cultures treated with high-concentration EGCG (50 microM). In addition, exposure to 50 microM EGCG or 400 microM GA for 24 hr led to a significant increase in fragmented DNA, but ECG did not significantly induce DNA fragmentation compared to the control. These results suggest that EGCG induces mostly apoptosis in OK cells, but the cellular toxicity of GA involves both apoptosis and other mechanisms. Finally, ECG inhibits the growth largely via some mechanism other than apoptosis. This chemical-specific difference of cytotoxic pattern may be dependent on the combination of GA and basal catechin structures, or NADH oxidase (NOX) activity on the OK cell surface.
Miyamoto
Yohei
Y
Toxicology Laboratory,Toray Industries, Inc. 1111, Tebiro, Kamakura, Kanagawa 248-8555, Japan.
Haylor
John L
JL
El Nahas
A Meguid
AM
D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000473:pathology; D009893:Opossums
D000975:Antioxidants; D005707:Gallic Acid; D002392:Catechin; C045651:epigallocatechin gallate