cardamonin and Carcinogenesis

Cardamonin (CAD) is a member of the aromatic ketones family that is closely related to anti-bacterial, anti-inflammatory and anti-cancer effects. Nevertheless, the physiological function of cardamonin in chronic colitis and colon cancer has not been well verified. We found that cardamonin treatment alleviates intestinal disease, including recurring colitis and colitis-associated tumorigenesis, along with the reduced secretion of IL-1β and TNF-α. Further, cardamonin inhibits cell viability and inflammation factors of colorectal cancer cells in vitro. In tumor cells, the inhibitory effect of cardamonin on cell proliferation is closely related to decreased phosphorylation of signal transducers and activators of transcription (STAT) signals. This study reveals the crucial role of cardamonin in sustaining gastrointestinal homeostasis and offers a new strategy for colon cancer therapy.

Topics: Animals; Carcinogenesis; Cell Survival; Chalcones; Colitis; Colon; Colonic Neoplasms; Dextran Sulfate; Disease Models, Animal; HT29 Cells; Humans; Inflammation; Interleukin-1beta; Neoplasm Recurrence, Local; NF-kappa B; Signal Transduction; STAT Transcription Factors; Tumor Necrosis Factor-alpha

Topics: Antineoplastic Agents; Apoptosis; Carcinogenesis; Cell Cycle; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chalcones; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; RNA, Long Noncoding; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms

Previous studies have shown that testes-specific protease 50 (TSP50), a pro-oncogene overexpressed in many types of tumors, could promote cell proliferation, invasion, tumorigenesis, and tumor metastasis, suggesting that it is a potential cancer therapeutic target in drug discovery. Here, a luciferase assay system driven by the TSP50 gene promoter was used to screen the inhibitor of expression of TSP50. The study found that cardamonin, a flavone compound, could efficiently inhibit the expression of TSP50 in both mRNA and protein levels. Further results revealed that cardamonin also efficiently inhibited the viability of TSP50 high-expressing cancer cells by inducing G2/M-phase arrest and mitochondrial-dependent apoptosis. Surprisingly, knocking down the expression of TSP50 gene had the same effects as treatment with cardamonin. Moreover, it has been found that cardamonin had an inhibitory potency on TSP50 high-expressing tumor growth in vivo. In contrast, overexpression of TSP50 greatly decreased the cell sensitivity to the inhibitory effect of cardamonin and reversed the decreased tumor-inhibitory effect of cardamonin. Additionally, both TSP50 interference and treatment with cardamonin could suppress p65 nuclear translocation, and overexpression of TSP50 reversed the suppressive effect of cardamonin on p65 nuclear translocation. Taken together, these results suggest that cardamonin inhibited cell viability and tumorigenesis at least partially via blocking the activation of TSP50-mediated nuclear factor-kappaB signaling pathway, and cardamonin may be a promising anticancer drug candidate in the development of a novel agent for TSP50 high-expressing cancer cells.

Topics: Apoptosis; Carcinogenesis; Cell Cycle; Cell Survival; Cell Transformation, Neoplastic; Chalcones; HEK293 Cells; Humans; In Situ Nick-End Labeling; Male; NF-kappa B; Promoter Regions, Genetic; Serine Endopeptidases; Signal Transduction; Testis