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DOI: 10.1055/s-0028-1088364
© Georg Thieme Verlag KG Stuttgart · New York
In vitro Antitumor Mechanisms of Various Scutellaria Extracts and Constituent Flavonoids
Publication History
Received: June 26, 2008
Revised: September 8, 2008
Accepted: September 12, 2008
Publication Date:
24 November 2008 (online)
![](https://www.thieme-connect.de/media/plantamedica/200901/lookinside/thumbnails/10.1055-s-0028-1088364-1.jpg)
Abstract
Scutellaria is a traditional herbal remedy with potential anti-cancer activity. The purpose of this study was to evaluate anticancer mechanisms of thirteen Scutellaria species and analyze their leaf, stem and root extracts for levels of common biologically active flavonoids: apigenin, baicalein, baicalin, chrysin, scutellarein, and wogonin. Malignant glioma, breast carcinoma and prostate cancer cells were used to determine tumor-specific effects of Scutellaria on cell proliferation, apoptosis and cell cycle progression, via the MTT assay and flow cytometry-based apoptosis and cell cycle analysis. The extracts and individual flavonoids inhibited the proliferation of malignant glioma and breast carcinoma cells without affecting primary or non-malignant cells. The flavonoids exhibited different mechanisms of anti-tumor activity as well as positive interactions. The antitumor mechanisms involved induction of apoptosis and cell cycle arrest at G1/G2. Of the extracts tested, leaf extracts of S. angulosa, S. integrifolia, S. ocmulgee and S. scandens were found to have strong anticancer activity. This study provides basis for further mechanistic and translational studies into adjuvant therapy of malignant tumors using Scutellaria leaf tissues.
Key words
Scutellaria - Lamiacae - flavonoid - malignant glioma - breast carcinoma - apoptosis - cell cycle
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References
- 1 Huang W H, Lee A R, Yang C H. Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis Georgi. Biosci Biotechnol Biochem. 2006; 70 2371-80
- 2 Nijveldt R J, van Nood E, van Hoorn D E, Boelens P G, van Norren K, van Leeuwen P A. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 2001; 74 418-25
- 3 Cole I B, Cao J, Alan A R, Saxena P K, Murch S J. Comparisons of Scutellaria baicalensis, Scutellaria lateriflora and Scutellaria racemosa: genome size, antioxidant potential and phytochemistry. Planta Med. 2008; 74 474-81
- 4 Awad R, Arnason J T, Trudeau V, Bergeron C, Budzinski J W, Foster B C. et al . Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine. 2003; 10 640-9
- 5 Ernst E. Herbal remedies for anxiety – a systematic review of controlled clinical trials. Phytomedicine. 2006; 13 205-8
- 6 Kumagai T, Muller C I, Desmond J C, Imai Y, Heber D, Koeffler H P. Scutellaria baicalensis, a herbal medicine: anti-proliferative and apoptotic activity against acute lymphocytic leukemia, lymphoma and myeloma cell lines. Leuk Res. 2007; 31 523-30
- 7 Scheck A C, Perry K, Hank N C, Clark W D. Anticancer activity of extracts derived from the mature roots of Scutellaria baicalensis on human malignant brain tumor cells. BMC Complement Altern Med [electronic resource]. 2006; 6 27
- 8 Ye F, Jiang S, Volshonok H, Wu J, Zhang D Y. Molecular mechanism of anti-prostate cancer activity of Scutellaria baicalensis extract. Nutr Cancer. 2007; 57 100-10
- 9 Zhang D Y, Wu J, Ye F, Xue L, Jiang , Yi J. et al . Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. . Cancer Res. 2003; 63 4037-43
- 10 Bonham M, Posakony J, Coleman I, Montgomery B, Simon J, Nelson P S. Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma. Clin Cancer Res. 2005; 11 3905-14
- 11 Kim E K, Kwon K B, Han M J, Song M Y, Lee J H, Ko Y S. et al . Induction of G1 arrest and apoptosis by Scutellaria barbata in the human promyelocytic leukemia HL-60 cell line. Int J Mol Med. 2007; 20 123-8
- 12 Yin X, Zhou J, Jie C, Xing D, Zhang Y. Anticancer activity and mechanism of Scutellaria barbata extract on human lung cancer cell line A549. Life Sci. 2004; 75 2233-44
- 13 Yu J, Liu H, Lei J, Tan W, Hu X, Zou G. Antitumor activity of chloroform fraction of Scutellaria barbata and its active constituents. Phytother Res. 2007; 21 817-22
- 14 Hsieh T C, Lu X, Chea J, Wu J M. Prevention and management of prostate cancer using PC-SPES: a scientific perspective. J Nutr. 2002; 132 3513S-7S
- 15 Rugo H, Shtivelman E, Perez A, Vogel C, Franco S, Tan Chiu E. et al . Phase I trial and antitumor effects of BZL101 for patients with advanced breast cancer. Breast Cancer Res Treat. 2007; 105 17-28
- 16 Hsu S L, Hsieh Y C, Hsieh W C, Chou C J. Baicalein induces a dual growth arrest by modulating multiple cell cycle regulatory molecules. Eur J Pharmacol. 2001; 425 165-71
- 17 Kyo R, Nakahata N, Sakakibara I, Kubo M, Ohizumi Y. Baicalin and baicalein, constituents of an important medicinal plant, inhibit intracellular Ca2+ elevation by reducing phospholipase C activity in C6 rat glioma cells. J Pharm Pharmacol. 1998; 50 1179-82
- 18 Ma Z, Otsuyama K, Liu S, Abroun S, Ishikawa H, Tsuyama N. et al . Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood. 2005; 105 3312-8
- 19 Lee S W, Song G S, Kwon C H, Kim Y K. Beneficial effect of flavonoid baicalein in cisplatin-induced cell death of human glioma cells. Neurosci Lett. 2005; 382 71-5
- 20 Ujiki M B, Ding X Z, Salabat M R, Bentrem D J, Golkar L, Milam B. et al . Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Mol Cancer. 2006; 5 76
- 21 Brusselmans K, Vrolix R, Verhoeven G, Swinnen J V. Induction of cancer cell apoptosis by flavonoids is associated with their ability to inhibit fatty acid synthase activity. J Biol Chem. 2005; 280 5636-45
- 22 Way T D, Kao M C, Lin J K. Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. J Biol Chem. 2004; 279 4479-89
- 23 Chang W H, Chen C H, Lu F J. Different effects of baicalein, baicalin and wogonin on mitochondrial function, glutathione content and cell cycle progression in human hepatoma cell lines. Planta Med. 2002; 68 128-32
- 24 Mathupala S P, Parajuli P, Sloan A E. Silencing of monocarboxylate transporters via small interfering ribonucleic acid inhibits glycolysis and induces cell death in malignant glioma: an in vitro study. Neurosurgery. 2004; 55 1410-9
- 25 Parajuli P, Mathupala S, Sloan A E. Systematic comparison of dendritic cell-based immunotherapeutic strategies for malignant gliomas: in vitro induction of cytolytic and natural killer-like T cells. Neurosurgery. 2004; 55 1194-204
- 26 Mantel N W. Haenszel. 1959. J Natl Cancer Inst. 1959; 22 719
- 27 Bergeron C, Gafner S, Clausen E, Carrier D J. Comparison of the chemical composition of extracts from Scutellaria lateriflora using accelerated solvent extraction and supercritical fluid extraction versus standard hot water or 70 % ethanol extraction. J Agric Food Chem. 2005; 53 3076-80
- 28 Bochorakova H, Paulova H, Slanina J, Musil P, Taborska E. Main flavonoids in the root of Scutellaria baicalensis cultivated in Europe and their comparative antiradical properties. Phytother Res. 2003; 17 640-4
- 29 Sonoda M, Nishiyama T, Matsukawa Y, Moriyasu M. Cytotoxic activities of flavonoids from two Scutellaria plants in Chinese medicine. J Ethnopharmacol. 2004; 91 65-8
- 30 Treutter D. Significance of flavonoids in plant resistance and enhancement of their biosynthesis. Plant Biol. 2005; 7 581-91
P. Parajuli, Ph.D.
Department of Neurosurgery
Wayne State University & Karmanos Cancer Institute
4100 John R. St.
HW-CRC #607
Detroit, MI 48201
USA
Phone: +1-313-576-8353
Fax: +1-313-576-8306
Email: pparajuli@med.wayne.edu
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