E1a-3y1 cell-specific toxicity of tea polyphenols and their killing mechanism
T Mitsui1, K Yamada, K Yamashita
1KYUSHU UNIV 69,MED INST BIOREGULAT,DEPT VIROL,HIGASHI KU,FUKUOKA 812,JAPAN. KYUSHU UNIV 46 09,FAC AGR,DEPT FOOD SCI & TECHNOL,FOOD SCI LAB,HIGASHI KU,FUKUOKA 812,JAPAN.
Abstract:
To screen carcinostatic components in foodstuffs, the toxicity of tea polyphenols was compared between rat 3Y1 diploid fibroblasts and a variety of their virally transformed cells. Among tea polyphenols tested, epigallocatechin gallate killed 3Y1 cells transformed by E1A gene of human adenovirus type 12 (E1A-3Y1 cells) at a 100 times lower concentration than the parental 3Y1 cells. Epigallocatechin gallate also exerted a strong E1A-3Y1 cell-specific toxicity, while epicatechin and epicatechin gallate did not. When the activity of three antioxidant enzymes was compared between 3Y1 and its transformants, catalase activity was markedly low in the latter, especially in E1A-3Y1 cells, and the substrate of the enzyme, hydrogen peroxide, exerted a toxicity specific to this cell line. Then the inhibitory activities of various chemicals on E1A-3Y1 cell-specific toxicity of phospholipids or catechol were examined. Among lipoxygenase inhibitors, all of the polyphenolic compounds inhibited the toxicity of phospholipids, but not a nonpolyphenolic inhibitor (clofibrate). Two phospholipase A,inhibitors (dexamethasone and quinacrine) did not inhibit the toxicity. These results indicate that the triphenol structure of the B ring is essential for the E1A-3Y1 cell-specific toxicity of tea polyphenols, and that the decrease in catalase activity is partially responsible for the higher sensitivity of E1A-3Y1 cells against the polyphenols. The inhibitory effect of polyphenolic lipoxygenase inhibitors is ascribed at least in part to their antioxidant activities.
Insights
Epigallocatechin gallate, a tea polyphenol, shows specific toxicity against E1A-3Y1 cells, a transformed cell line. This targeted effect is linked to reduced catalase activity in these cells, suggesting potential for cancer research.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Carcinostatic components in foodstuffs are of interest for cancer research.
- Tea polyphenols are known for their diverse biological activities.
- Viral transformation of cells can alter their susceptibility to cytotoxic agents.
Purpose of the Study:
- To screen tea polyphenols for carcinostatic properties.
- To investigate the specific toxicity of tea polyphenols against virally transformed cells.
- To elucidate the mechanisms underlying the differential sensitivity of normal and transformed cells to tea polyphenols.
Main Methods:
- Comparison of tea polyphenol toxicity between rat 3Y1 diploid fibroblasts and virally transformed cell lines (E1A-3Y1).
- Assay of antioxidant enzyme activities (catalase) in normal and transformed cells.
- Examination of inhibitory effects of various chemicals on cell-specific toxicity.
Main Results:
- Epigallocatechin gallate demonstrated 100-fold greater toxicity against E1A-3Y1 cells compared to parental 3Y1 cells.
- Reduced catalase activity was observed in E1A-3Y1 cells, with hydrogen peroxide exhibiting specific toxicity.
- Polyphenolic lipoxygenase inhibitors, but not non-polyphenolic ones, inhibited phospholipid toxicity, suggesting the B ring's triphenol structure is crucial.
Conclusions:
- Epigallocatechin gallate exhibits specific toxicity towards E1A-3Y1 cells, indicating potential as a carcinostatic agent.
- Decreased catalase activity in transformed cells contributes to their heightened sensitivity to tea polyphenols.
- The antioxidant activity of polyphenolic lipoxygenase inhibitors plays a role in their inhibitory effects.
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