Treating colorectal cancer patients commonly involves several conventional modalities, including surgery, radiation, and chemotherapy. The complexity of colorectal cancer, however, requires additional alternatives to improve the therapeutic efficacy of conventional treatment and the quality of life of cancer patients. Medicinal botanicals have recently gained attention as additions to colorectal cancer management. Numerous effective anticancer drugs have been developed from botanicals, and identifying new herbal sources for ideal chemoprevention remains essential to advance the treatment of colorectal cancer. Scutellaria baicalensis extract (SbE) has chemopreventive effects on several cancers. Baicalin, a major constituent of SbE, also may have the negative effect of decreasing the anti-tumor potential of SbE. In this study, we prepared a baicalin knockout fraction (BKF) of SbE and evaluated its antiproliferative activity and mechanism of action. The constituents of BKF, baicalin fraction (BF), and SbE were quantified by HPLC. We then used an MTS assay to determine the effects of BKF, BF, SbE, and the representative flavonoids on the proliferation of human colorectal cancer cells (HCT-116 and HT-29). Cell cycle, cyclin A expression and cell apoptosis were assayed by flow cytometry. Apoptosis-related gene expression was visualized by quantitative real-time polymerase chain reaction (PCR), and mitochondrial membrane potential was estimated after staining with JC-1. HPLC analysis showed that BKF contained baicalein and wogonin; BF contained only baicalin. SbE had little antiproliferative effect on cancer cells, even increasing cancer cell growth at certain concentrations. BF increased cancer cell growth. BKF showed potent antiproliferative effects on cancer cells. BKF arrested cells in the S and G2/M phases, increased expression of cyclin A, and significantly induced cell apoptosis. Multiple genes in the mitochondrial pathway were involved in BKF-induced apoptosis, and subsequent cellular functional analysis validated the pathway. These results suggest that knocking out baicalin from SbE produces a BKF that significantly inhibits the growth of colorectal cancer cells. The active anticancer compounds in SbE are flavonoid aglycons, baicalein and wogonin, and the mitochondrial apoptotic pathway is part of baicalein and wogonin-induced apoptosis. (This work was supported in part by the NIH/NCCAM grants AT004418 and AT005362).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1975. doi:1538-7445.AM2012-1975