Alkaloid Compound Cardamonin Induces Growth Suppression Of Human Colon Adenocarcinoma HT29Cells In Vitro

Colon cancer is the most common primary intestinal malignancy andthe third prevalent cancer worldwide. Lack of compliance with screeningmethods is the reason for a huge number of cases being diagnosed inadvanced stages where chemotherapy in the adjuvant or palliative setting isrecommended. Most colorectal cancers show resistance to anticancer drugsclinically and experimentally. The clinical use of chemotherapeutic drugsin cancer treatment is limited, however. It was well established that whenpatients received surgery alone, the survival rate would be quite low.Recently, thanks to the development of chemotherapy against colon cancer,the5-year survival rate of colon cancer patients has been significantlyimproved. Neverthless, due to the high motility and increasing drugresistance of colon cancer, the outcomes of existing conventionalchemotherapeutic drugs remain considerably low. Therefore, emergingstudies have focused on extracts of traditional medicine to search for highlyefficient anticancer drugs with low toxicity.Cardamonin (22,42-dihydroxy-62-methoxychalcone) is a chalconethat derived from large black cardamom (fruit of Amomum subulatum).Increasing number of studies demonstrated that cardamonin regulate cellgrowth by activation of a variety of cell signalling pathways, including mTOR(mammalian target of rapamycin) signaling pathway, NF-kB signaltransduction and Wnt/β-catenin signaling. This chalcone has also beenshown to bind to lysozyme and human serum albumin. Pretreatment withcardamomin has also been shown to protect mice from LPS-inducedmortality in association with decreased serum levels of TNF-a, IL-6andIL-1b secretion. Hereby, we hypothesized that its anticancer activityinvolves mitochondrial apoptotic pathway that triggered by a series ofapoptosis factors.In this regard, we investigated the impacts of cardamonin on theproliferative ability of colon cancer cell line HT-29in vitro through MTTassay method. In addition, flow cytometry analysis was implemented tomeasure the proapoptotic effect of the alkaloid compnent on tumor cellapoptosis and ROS level. Finally, we did perform western blotting assay todetermine the expression level of apoptosis modulators, including P53.Taken together, our data demonstrated that cardamonin suppress theproliferation of colon cancer cells in vitro via inducing mitochodrialapoptosis. Its proapoptotic property involves the activation of a series ofapoptosis factors, including P53protein and Bax/Bcl-2ratio. These resultswill help us understand the molecular mechanism underlying anticanceractivity of cardamonin and provide reliable clues to exploit new drugs.These findings were firstly reported in the present study.