Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma. Clin Cancer Res

University of Washington Seattle, Seattle, Washington, United States
Clinical Cancer Research (Impact Factor: 8.72). 05/2005; 11(10):3905-14. DOI: 10.1158/1078-0432.CCR-04-1974
Source: PubMed


Botanical preparations are widely used by patients with prostate cancer. Scutellaria baicalensis, a botanical with a long history of medicinal use in China, was a constituent of the herbal mixture PC-SPES, a product that inhibited prostate cancer growth in both laboratory and clinical studies. Due to the difficulties encountered when evaluating the efficacy of complex natural products, we sought to identify active chemical constituents within Scutellaria and determine their mechanisms of action.
We used high-performance liquid chromatography to fractionate S. baicalensis and identified four compounds capable of inhibiting prostate cancer cell proliferation; baicalein, wogonin, neobaicalein, and skullcapflavone. Comparisons of the cellular effects induced by the entire extract versus the four-compound combination produced comparable cell cycle changes, levels of growth inhibition, and global gene expression profiles (r(2) = 0.79). Individual compounds exhibited antiandrogenic activities with reduced expression of the androgen receptor and androgen-regulated genes. In vivo, baicalein (20 mg/kg/d p.o.) reduced the growth of prostate cancer xenografts in nude mice by 55% at 2 weeks compared with placebo and delayed the average time for tumors to achieve a volume of approximately 1,000 mm(3) from 16 to 47 days (P < 0.001).
Most of the anticancer activities of S. baicalensis can be recapitulated with four purified constituents that function in part through inhibition of the androgen receptor signaling pathway. We conclude that clinical studies evaluating the efficacy of these agents in the context of chemoprevention or the treatment of prostate cancer are warranted.

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    • "HLJDT is prepared from boiled water extracts of four medicinal herbs in equal ratio, namely, Coptis chinensis Franch (黃連 Huáng Lián), Scutellaria baicalensis Georgi (黃芩 Huáng Qín), Phellodendron amurense Ruprecht (黃柏 Huáng Bǎi), and Gardenia jasminoides Ellis (山黃槴 Shān Huáng Huā) [Table 1]. Molecular constituents of HLJDT have been shown to possess antitumor properties, and bioactive compounds such as berberine, genipin, baicalein, and wogonin have been associated with inhibition of cancer cell growth, regulation of cell cycle, as well as induction of apoptosis.[52535455565758] Our previous study has shown that HLJDT can inhibit the human hepatoma HepG2 and PLC/PRF/5 cell proliferation in vitro and restrict the hepatoma cell-induced tumor growth in nude mice.[59] "
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    ABSTRACT: Hepatocellular carcinoma (HCC) has long been one of the most important causes of cancer mortality in the world. Many natural products and traditional herbal medicines have been used to treat HCC in Asian countries such as Japan, Korea, Taiwan, and China. The present review aims to describe the anticancer properties and apoptotic mechanisms of cinnamaldehyde, the bioactive ingredient isolated from cinnamon trees, and the herbal prescription Huang-Lian-Jie-Du-Tang ( Huáng Lián Jiě Dú Tang; HLJDT) against human hepatoma cells in vitro and in vivo. Implication of their treatment for the development of targeted therapy against HCC is discussed.
    No preview · Article · Mar 2013 · Journal of Traditional and Complementary Medicine
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    • "The effect of S. baicalensis on human colorectal cancer remains uncertain; a limited anti-proliferative effect of SbE on human colorectal cancer cells has been reported. Compared to its effect on liver and prostate cancer lines (9,10), the anti-proliferative activity of SbE on human colorectal cancer cells is limited (11,12). Although baicalein inhibits the growth of colon cancer cells (13,14), no such results have been obtained with baicalin, the major constituent of SbE. "
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    ABSTRACT: Scutellaria baicalensis extract (SbE) has been shown to exert chemopreventive effects on several types of cancer. Baicalin, a hydrophilic flavonoid found in SbE, may have opposing effects that decrease the antitumor potential of SbE against colorectal cancer. In this study, after removing baicalin, we prepared an aglycone-rich fraction (ARF) of SbE and evaluated its anti-proliferative activity and mechanisms of action. The flavonoids found in ARF, baicalin fraction (BF) and SbE were determined by high-performance liquid chromato-graphy (HPLC). The effects of ARF, BF, SbE and representative flavonoids on the proliferation of HCT-116 and HT-29 human colorectal cancer cells were determined by an MTS assay. The cell cycle, the expression of cyclins A and B1 and cell apoptosis were assayed using flow cytometry. Apoptosis-related gene expression was visualized by quantitative real-time polymerase chain reaction (PCR), and mitochondrial membrane potential was estimated following staining with JC-1. HPLC analysis showed that ARF contained two hydrophobic flavonoids, baicalein and wogonin, and that BF contained only baicalin. SbE had little anti-proliferative effect on the colorectal cancer cells; cancer cell growth was even observed at certain concentrations. ARF exerted potent anti-proliferative effects on the cancer cells. By contrast, BF increased cancer cell growth. ARF arrested cells in the S and G2/M phases, increased the expression of cyclins A and B1, and significantly induced cell apoptosis. Multiple genes in the mitochondrial pathway are involved in ARF-induced apoptosis, and subsequent cellular functional analysis validated the involvement of this pathway. These results suggest that removing baicalin from SbE produces an ARF that significantly inhibits the growth of colorectal cancer cells, and that the mitochondrial apoptotic pathway plays a role in hydrophobic flavonoid-induced apoptosis.
    Full-text · Article · Jan 2013 · International Journal of Oncology
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    • "The only growth inhibition assay that has been carried out with neobaicalein was done on the LNCaP and PC-3 cells (Bonham et al., 2005). Neobaicalein-mediated inhibition of HeLa cells growth has not been described before, although wogonin has been reported to reduce the proliferation of several cell types (Ikemoto et al., 2000; Sonoda et al., 2004) including HeLa cells (Yang et al., 2009; Yu et al., 2007). "
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    ABSTRACT: Chemical investigation on the CH2Cl2 fraction of the Scutellaria litwinowii Bornm. & Sint., Lamiaceace, root extract for the first time resulted in the isolation of wogonin, and neobaicalein. These compounds were evaluated for their cytotoxicity towards HeLa cell lines and lymphocytes. Meanwhile, the role of apoptosis was explored in this toxicity. The cells were cultured in RPMI medium and incubated with different concentrations of isolated flavonoids. Cell viability was quantified by MTS assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1peak). Wogonin, and neobaicalein inhibited the growth of malignant cells in a dose-dependent manner. The IC50 values of 46.62 and 79.34 µM were, respectively, found for neobaicalein and wogonin against HeLa cells after 48 h of treatment. Neobaicalein induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in neobaicalein toxicity. Neobaicalein exerts cytotoxic and pro-apoptotic effects in HeLa cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.
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