Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces apoptosis and cell cycle arrest in human colon cancer HCT116 cells.
Because of unsatisfactory treatment options for colon cancer, there is a need to develop novel preventive approaches for this malignancy. One such strategy is through chemoprevention by the use of non-toxic dietary substances and botanical products. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, possesses strong anti-oxidant and anti-inflammatory properties. In the present study, we investigated the antiproliferative and proapoptotic properties of delphinidin in human colon cancer HCT116 cells. We found that treatment of cells with delphinidin (30-240 microM; 48 h) resulted in (i) decrease in cell viability (ii) induction of apoptosis, (iii) cleavage of PARP, (iv) activation of caspases-3, -8, and -9, (v) increase in Bax with a concomitant decrease in Bcl-2 protein, and (vi) G2/M phase cell cycle arrest. NF-kappaB provides a mechanistic link between inflammation and cancer, and is a major factor controlling the ability of both pre-neoplastic and malignant cells to resist apoptosis-based tumor surveillance mechanisms. We therefore, determined the effect of delphinidin on NF-kappaB signaling pathway. The immunoblot, ELISA and EMSA analysis demonstrated that the treatment of HCT116 cells with delphinidin resulted in the inhibition of (i) IKKalpha, (ii) phosphorylation and degradation of IkappaBalpha, (iii) phosphorylation of NF-kappaB/p65 at Ser(536), (iv) nuclear translocation of NF-kappaB/p65, (v) NF-kappaB/p65 DNA binding activity, and (vi) transcriptional activation of NF-kappaB. Our results suggest that delphinidin treatment of HCT116 cells suppressed NF-kappaB pathway, resulting in G2/M phase arrest and apoptosis. We suggest that delphinidin could have potential in inhibiting colon cancer growth.
Yun
Jung-Mi
JM
Department of Dermatology, University of Wisconsin, Madison, Wisconsin.
Afaq
Farrukh
F
Department of Dermatology, University of Wisconsin, Madison, Wisconsin.
Khan
Naghma
N
Department of Dermatology, University of Wisconsin, Madison, Wisconsin.
Mukhtar
Hasan
H
Department of Dermatology, University of Wisconsin, Madison, Wisconsin.
D000872:Anthocyanins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation; D024161:Collagen Type XI / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005638:Fruit; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010944:Plants; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014675:Vegetables; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000872:Anthocyanins; C494826:BAX protein, human; C499319:COL11A2 protein, human; D024161:Collagen Type XI; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000072000:NF-KappaB Inhibitor alpha; D053148:Caspase 3; C017185:delphinidin