Green tea polyphenol targets the mitochondria in tumor cells inducing caspase 3-dependent apoptosis.
Induction of apoptosis by green tea polyphenols has been observed in various tumor cell systems, but whether green tea polyphenol-induced apoptosis requires caspase 3 for execution has not been confirmed. We previously reported that green tea polyphenol-induced apoptosis involved Apaf-1 accumulation and caspase 3 activation in the cytosol. In the current study, tumor cells either with deleted caspase 3 gene or expressing wild-type caspase 3 were treated with increasing concentrations of green tea polyphenol(s), followed by morphological analysis and caspase 3 activity assay. The caspase 3 null parental cell line was further examined in comparison with a well-characterized, caspase 3 wild type oral carcinoma cell line by MTT assay and BrdU incorporation assay. The results demonstrated that, while the mitochondrial function gradually declined to insignificant levels, caspase 3 null cells did not undergo apoptosis, which suggested that green tea polyphenol-induced apoptosis is a mitochondria-targeted, caspase 3-executed mechanism.
Hsu
Stephen
S
Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, AD1443. Medical College of Georgia, Augusta, GA 30912-1126, USA. shsu@mail.mcg.edu
Lewis
Jill
J
Singh
Baldev
B
Schoenlein
Patricia
P
Osaki
Tokio
T
Athar
Mohammad
M
Porter
Alan G
AG
Schuster
George
G
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1; D001859:Bone Neoplasms / Q000201:enzymology / Q000473:pathology; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000556:secondary; D053148:Caspase 3; D020169:Caspases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D005419:Flavonoids; D017353:Gene Deletion; D005887:Gingival Neoplasms / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008207:Lymphatic Metastasis; D008928:Mitochondria / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D005419:Flavonoids; D009363:Neoplasm Proteins; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D011506:Proteins; D013662:Tea; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C057580:gallocatechol