Hydrophobic flavonoids from Scutellaria baicalensis induce colorectal cancer cell apoptosis through a mitochondrial-mediated pathway

Wang,Chong-Zhi; Calway,Tyler  D.; Wen,Xiao-Dong; Smith,Jacob; Yu,Chunhao; Wang,Yunwei; Mehendale,Sangeeta  R.; Yuan,Chun-Su

doi:10.3892/ijo.2013.1777

Hydrophobic flavonoids from Scutellaria baicalensis induce colorectal cancer cell apoptosis through a mitochondrial-mediated pathway

Authors:
- Chong-Zhi Wang
- Tyler D. Calway
- Xiao-Dong Wen
- Jacob Smith
- Chunhao Yu
- Yunwei Wang
- Sangeeta R. Mehendale
- Chun-Su Yuan
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Affiliations: Tang Center for Herbal Medicine Research, and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
Published online on: January 16, 2013 https://doi.org/10.3892/ijo.2013.1777
Pages: 1018-1026

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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 chromatography (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.

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