5-7-dihydroxy-6-methoxy-2-phenylchromen-4-one and Adenocarcinoma

Oroxylin A is a flavonoid found in the roots of Scutellaria baicalensis Georgi, a herbal medicine commonly used as an antipyretic, analgesic, antitumor, and anti-inflammatory agent. It has recently been investigated for its anticancer activities in hepatoma, gastric, and breast tumors. Here, we investigated the antitumor effects of oroxylin A in human colon carcinoma HCT-116 cells in vitro and in vivo. We characterized the proapoptotic effect of oroxylin A using diamidino-phenyl-indole (DAPI) and annexin V/PI staining. We then found that both caspase-3 and caspase-9 were activated, the expression of Bcl-2 protein decreased, and the expression of Bax protein increased after treatment with oroxylin A. In addition, oroxylin A increased nuclear transcription factor erythroid-related factor 2 (Nrf2) expression and induced Nrf2 translocation into the nucleus. Furthermore, we found that oroxylin A treatment elevated intracellular reactive oxygen species levels and increased the protein expression level of two of the Nrf2 target genes heme oxygenase-1 and NADP(H):quinone oxidoreductase-1 in HCT-116 cells. Finally, our study demonstrated that oral administration of oroxylin A significantly decreased tumor volume and weight in immunodeficient mice that were inoculated with HCT-116 cells. The in-vivo chemopreventive efficacy of oroxylin A against HCT-116 human colon cancer was accompanied by its proapoptotic and Nrf2-inducing activities, which correlates with the in-vitro study. This is the first demonstration of oroxylin A-dependent chemoprevention in colon cancer and may offer a potential mechanism for its anticancer action in vivo.

Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Nucleus; Colorectal Neoplasms; Flavonoids; Gene Expression Regulation, Neoplastic; HCT116 Cells; Heme Oxygenase-1; Humans; Male; Mice; Mice, Inbred BALB C; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Protein Transport; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Xenograft Model Antitumor Assays