title: Bioactive proanthocyanidins inhibit growth and induce apoptosis in human melanoma cells by decreasing the accumulation of β-catenin.
abstract: Melanoma is a highly aggressive form of skin cancer with poor survival rate. Aberrant activation of Wnt/β-catenin has been observed in nearly one-third of human melanoma cases thereby indicating that targeting Wnt/β-catenin signaling could be a promising strategy against melanoma development. In the present study, we determined chemotherapeutic effect of grape seed proanthocyanidins (GSPs) on the growth of melanoma cells and validated their protective effects in vivo using a xenograft mouse model, and assessed if β-catenin is the target of GSP chemotherapeutic effect. Our in vitro data show that treatment of A375 and Hs294t human melanoma cells with GSPs inhibit the growth of melanoma cells, which was associated with the reduction in the levels of β-catenin. Administration of dietary GSPs (0.2 and 0.5%, w/w) in supplementation with AIN76A control diet significantly inhibited the growth of melanoma tumor xenografts in nude mice. Furthermore, dietary GSPs inhibited the xenograft growth of Mel928 (β-catenin-activated), while did not inhibit the xenograft growth of Mel1011 (β-catenin-inactivated) cells. These observations were further verified by siRNA knockdown of β-catenin and forced overexpression of β-catenin in melanoma cells using a cell culture model.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, AL 35294, USA.
authors.forename: Mudit
authors.initials: M
authors.lastname: Vaid
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, AL 35294, USA.
authors.forename: Tripti
authors.initials: T
authors.lastname: Singh
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, AL 35294, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, AL 35294, USA.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D044945:Proanthocyanidins / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D051176:beta Catenin