ABSTRACT
Cardamonin is a naturally occurring chalcone, majorly from the Zingiberaceae family, which includes a wide range of spices from India. Herein, we investigated the anti-inflammatory property of cardamonin using different in vitro and in vivo systems. In RAW 264.7 cells, treatment with cardamonin showed a reduced nitrous oxide production without affecting the cell viability and decreased the expression of iNOS, TNF-α, and IL-6, and inhibited NF-kB signaling which emphasizes the role of cardamonin as an anti-inflammatory molecule. In a mouse model of dextran sodium sulfate (DSS)-induced colitis, cardamonin treatment protected the mice from colitis. Subsequently, we evaluated the therapeutic potential of this chalcone in a colitis-associated colon cancer model. We performed microRNA profiling in the different groups and observed that cardamonin modulates miRNA expression, thereby inhibiting tumor formation. Together, our findings indicate that cardamonin has the potential to be considered for future therapy against colorectal cancer.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Chalcones/administration & dosage , Colitis/drug therapy , Colorectal Neoplasms/drug therapy , MicroRNAs/genetics , Animals , Anti-Inflammatory Agents/pharmacology , Azoxymethane/adverse effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Chalcones/pharmacology , Colitis/chemically induced , Colitis/complications , Colitis/metabolism , Colorectal Neoplasms/etiology , Colorectal Neoplasms/genetics , Dextran Sulfate/adverse effects , Disease Models, Animal , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells , Humans , Mice , Nitrous Oxide/metabolism , RAW 264.7 Cells , Sequence Analysis, RNA , Signal Transduction/drug effects , THP-1 CellsABSTRACT
Colorectal cancer is currently the third leading cause of cancer related deaths. There is considerable interest in using dietary intervention strategies to prevent chronic diseases including cancer. Cardamonin is a spice derived nutraceutical and herein, for the first time we evaluated the therapeutic benefits of cardamonin in Azoxymethane (AOM) induced mouse model of colorectal cancer. Mice were divided into 4 groups of which three groups were given six weekly injections of AOM. One group served as untreated control and remaining groups were treated with either vehicle or Cardamonin starting from the same day or 16 weeks after the first AOM injection. Cardamonin treatment inhibited the tumor incidence, tumor multiplicity, Ki-67 and ß-catenin positive cells. The activation of NF-kB signaling was also abrogated after cardamonin treatment. To elucidate the mechanism of action a global microRNA profiling of colon samples was performed. Computational analysis revealed that there is a differential expression of miRNAs between these groups. Subsequently, we extend our findings to human colorectal cancer and found that cardamonin inhibited the growth, induces cell cycle arrest and apoptosis in human colorectal cancer cell lines. Taken together, our study provides a better understanding of chemopreventive potential of cardamonin in colorectal cancer.
