Epigallocatechin 3-O-gallate induces 67 kDa laminin receptor-mediated cell death accompanied by downregulation of ErbB proteins and altered lipid raft clustering in mammary and epidermoid carcinoma cells.
Since the administration of synthetic medicines is associated with drug resistance and undesired side effects, utilization of natural compounds could be an alternative and complementary modality to inhibit or prevent the development of tumors. Epigallocatechin 3-O-gallate (EGCG, 1), the major flavan component of green tea, and genistein (2), a soy isoflavonoid, are known to have chemopreventive and chemotherapeutic effects against cancer. This study demonstrated that both flavonoids inhibit cell proliferation, an effect enhanced under serum-free conditions. Compound 1, but not 2, induced downregulation of ErbB1 and ErbB2 in mammary and epidermoid carcinoma cells, and its inhibitory effect on cell viability was mediated by the 67 kDa laminin receptor (67LR). While 1 was superior in inducing cell death, 2 was more efficient in arresting the tumor cells in the G2/M phase. Furthermore, number and brightness analysis revealed that 1 decreased the homoclustering of a lipid raft marker, glycosylphosphatidylinositol-anchored GFP, and it also reduced the co-localization between lipid rafts and 67LR. The main conclusion made is that the primary target of 1 may be the lipid raft component of the plasma membrane followed by secondary changes in the expression of ErbB proteins. Compound 2, on the other hand, must have other unidentified targets.
Department of Biophysics, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy , 050474 Bucharest, Romania.
Maria-Magdalena
MM
Mocanu
Constanţa
C
Ganea
Laura
L
Georgescu
Tímea
T
Váradi
Dilip
D
Shrestha
Irina
I
Baran
Eva
E
Katona
Peter
P
Nagy
János
J
Szöllősi
D000465:Algorithms; D016588:Anticarcinogenic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D018773:Genes, erbB-1 / Q000235:genetics / Q000502:physiology; D018734:Genes, erbB-2 / Q000235:genetics / Q000502:physiology; D019833:Genistein / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D059808:Polyphenols / Q000494:pharmacology; D017474:Receptors, Laminin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012269:Ribosomal Proteins / Q000187:drug effects*; D013025:Glycine max / Q000737:chemistry; D013662:Tea / Q000737:chemistry*
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D059808:Polyphenols; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D019833:Genistein; D066246:ErbB Receptors; C057580:gallocatechol