New therapeutic aspects of flavones: The anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin
ABSTRACT Traditional Chinese medicines have been recently recognized as a new source of anticancer drugs and new chemotherapy adjuvant to enhance the efficacy of chemotherapy and to ameliorate the side effects of cancer chemotherapies however their healing mechanisms are still largely unknown. Scutellaria baicalensis is one of the most popular and multi-purpose herb used in China traditionally for treatment of inflammation, hypertension, cardiovascular diseases, and bacterial and viral infections. Accumulating evidence demonstrate that Scutellaria also possesses potent anticancer activities. The bioactive components of Scutellaria have been confirmed to be flavones. The major constituents of Scutellaria baicalensis are Wogonin, Baicalein and Baicalin. These phytochemicals are not only cytostatic but also cytotoxic to various human tumor cell lines in vitro and inhibit tumor growth in vivo. Most importantly, they show almost no or minor toxicity to normal epithelial and normal peripheral blood and myeloid cells. The antitumor functions of these flavones are largely due to their abilities to scavenge oxidative radicals, to attenuate NF-kappaB activity, to inhibit several genes important for regulation of the cell cycle, to suppress COX-2 gene expression and to prevent viral infections. The tumor-selectivity of Wogonin has recently been demonstrated to be due to its ability to differentially modulate the oxidation-reduction status of malignant vs. normal lymphocytic cells and to preferentially induce phospholipase C gamma 1, a key enzyme involved in Ca(2+) signaling, through H(2)O(2) signaling in malignant lymphocytes. This review is aimed to summarize the research results obtained since the last 20 years and to highlight the recently discovered molecular mechanisms.
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ABSTRACT: Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized.Cancer Letters 08/2014; DOI:10.1016/j.canlet.2014.08.003 · 5.02 Impact Factor
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ABSTRACT: Biocatalysts are a valuable tool for the structural modification of fine chemicals. Flavonoids possess several biological activities, which are correlated to their antioxidant activity. The numbers of hydroxyl groups in flavonoids are critical for their antioxidant activity. Development of biocatalysts for hydroxylation of flavonoids is challenging because of the difficulty in expressing flavonoid hydroxylase in Escherichia coli. In this study, a monooxygenase from Saccharothrix espanaensis (Sam5) was used for regioselective hydroxylation of flavonoids. We found that Sam5 hydroxylated isoflavones, flavanones, and flavones but did not produce any detectable hydroxylated product with flavonols. In addition, coexpression of P450 reductase with Sam5 in E. coli enhanced hydroxylation by approximately from 34 to 50%, depending on the flavonoid used. The production of two bioactive flavonoids, 8-hydroxyluteolin and 3′-hydroxydaidzein was optimized using this Sam5 system. Approximately 88 mg/L of 8-hydroxyluteolin and 75 mg/L of 3′-hydroxydaidzein were obtained. These results indicate that the Sam5 system could be used for the production of bioactive hydroxylated flavonoids.Journal of Biotechnology 04/2014; 176. DOI:10.1016/j.jbiotec.2014.02.002 · 2.88 Impact Factor
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ABSTRACT: Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of 1-75μg/mL. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.Asian Pacific journal of cancer prevention: APJCP 12/2013; 14(12):7179-86. DOI:10.7314/APJCP.2013.14.12.7179 · 2.51 Impact Factor