Antiproliferative and apoptosis-inducing activities of alkyl gallate and gallamide derivatives related to (−)-epigallocatechin gallate

Add time:07/30/2019    Source:sciencedirect.com

Green tea and (−)-epigallocatechin gallate (EGCG: one of the main components of green tea) are reported to have cancer-preventive activity in humans. A previous SAR study of EGCG and derivatives indicated that a galloyl group is essential for the activity. To test this hypothesis, we synthesized various alkyl gallate and gallamide derivatives and evaluated their antiproliferative effects on human leukemia HL-60 cells. Dodecyl 3,4,5-trihydroxybenzoate (6c) showed the most potent activity, being more potent than EGCG. To clarify the molecular mechanism of the antiproliferative action, we investigated the effects of 6c on various factors. Compound 6c was found to induce apoptosis mediated by endoplasmic reticulum (ER)-stress-related caspase-12. Upregulation of gadd-153, an ER-stress marker protein, was also observed. These results indicate that 6c induced apoptosis via the ER-stress-related pathway.

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