Genistein induces the metastasis suppressor kangai-1 which mediates its anti-invasive effects in TRAMP cancer cells.
Previous studies demonstrated a direct correlation with loss of kangai-1 (KAI1), a metastasis suppressor, and poor prognosis in human prostate and other cancers. In this study, we have characterized the age-dependent downregulation of KAI1 in the TRAMP model which was reversed when mice were fed a genistein-enriched diet. We demonstrated here that doses of genistein (5 and 10 microM)--achievable by supplement intake--significantly induced the expression of KAI1, both at the mRNA and protein levels (up to 2.5-fold), and decreased the invasiveness of TRAMP-C2 cells >2.0-fold. We have pinpointed KAI1 as the invasion suppressor, since its knockdown by siRNA restored the invasive potential of genistein-treated TRAMP-C2 cells to control levels. This work provides the first evidence that genistein treatment may counteract KAI1 downregulation, which is observed in many cancer types and therefore, could be used in anti-metastatic therapies.
Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Medical-Dental Building, 3900 Reservoir Road, NW, Washington, DC 20057, USA.
Lara H
LH
El Touny
Partha P
PP
Banerjee
D000367:Age Factors; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D019833:Genistein / Q000494:pharmacology*; D051861:Kangai-1 Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference
D016588:Anticarcinogenic Agents; D051861:Kangai-1 Protein; D019833:Genistein