The green tea polyphenol, epigallocatechin-3-gallate inhibits telomerase and induces apoptosis in drug-resistant lung cancer cells.
Epidemiological studies on humans and investigations in animal models suggest that consumption of green tea has anti-cancer effects. Small-cell lung carcinoma (SCLC) has a poor prognosis, particularly due to the development of drug resistance. We investigated the effects of the green tea polyphenol, epigallocatechin-3-gallate (EGCG) on human SCLC cells. EGCG had similar effects (IC(50) of approximately 70 microM) on drug-sensitive (H69) and drug-resistant (H69VP) SCLC cells, indicating that it is not part of the drug resistance phenotype expressed in these cells. In both cell lines, incubation in EGCG at 1 x IC(50) for 24h resulted in 50-60% reduced telomerase activity as measured by a PCR-based assay for telomeric repeats. Colorimetric assays of cells treated for 36 h with EGCG demonstrated a reduction in activities of caspases 3 (50%) and 9 (70%) but not caspase 8, indicating initiation of apoptosis. DNA fragmentation as measured by ELISA occurred within cells treated with EGCG and this was confirmed by TUNEL staining. Flow cytometric analysis of SCLC cells incubated for 36 h in EGCG indicated a cell-cycle block in S phase. These data indicate the potential use of EGCG, and possibly green tea, in treating SCLC.
Sadava
David
D
Keck Science Center, 925 North Mills Avenue, Claremont, CA, 91711, USA. dsadava@jsd.claremont.edu
Whitlock
Elizabeth
E
Kane
Susan E
SE
D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D010936:Plant Extracts / Q000008:administration & dosage; D019098:Telomerase / Q000037:antagonists & inhibitors*
D016588:Anticarcinogenic Agents; D010936:Plant Extracts; D002392:Catechin; C045651:epigallocatechin gallate; D019098:Telomerase