Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies

Cancer Letters

Volumn 354, Issue 1, 2014, Pages 5-11

  Chen, Haijun ^a,c   Gao, Yu ^a   Wu, Jianlei ^a   Chen, Yingyu ^b   Chen, Buyuan ^b   Hu, Jianda ^b   Zhou, Jia ^c  

^a FUZHOU UNIVERSITY   (China)

^b FUJIAN MEDICAL UNIVERSITY   (China)

^c University of Texas Medical Branch School of Medicine   (United States)

Author keywords

Baicalein; Baicalin; Cancer targets; Flavonoids; Hematological malignancies

Indexed keywords

AGLYCONE; BAICALEIN; BAICALIN; CASPASE 8; CASPASE 9; FLAVONOID; HERBACEOUS AGENT; NATURAL PRODUCT; POLYPHENOL DERIVATIVE; PROTEIN BAX; PROTEIN BCL XL; VINCRISTINE; ANTINEOPLASTIC AGENT; FLAVANONE DERIVATIVE; PLANT EXTRACT; POLYPHENOL;

ANTIDIABETIC ACTIVITY; ANTIFUNGAL ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; CHEMOPROPHYLAXIS; DRUG BIOAVAILABILITY; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; DRUG TOLERABILITY; EARLY DIAGNOSIS; ENTEROHEPATIC CIRCULATION; FIRST PASS EFFECT; HEMATOLOGIC MALIGNANCY; HUMAN; HYDROPHILICITY; IC50; LEUKEMIA; LIPOPHILICITY; LYMPHOMA; MYELOMA; SCUTELLARIA BAICALENSIS; SHORT SURVEY; SURVIVAL RATE; TRADITIONAL MEDICINE; BIOAVAILABILITY; BIOTRANSFORMATION; CANCER TARGETS; CHEMISTRY; DIET; DRUG DEVELOPMENT; HEMATOLOGIC DISEASE; HEMATOLOGICAL MALIGNANCIES; REVIEW; SIGNAL TRANSDUCTION;

BAICALEIN; BAICALIN; CANCER TARGETS; FLAVONOIDS; HEMATOLOGICAL MALIGNANCIES;

ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; BIOTRANSFORMATION; DIET; DRUG DISCOVERY; FLAVANONES; FLAVONOIDS; HEMATOLOGIC NEOPLASMS; HUMANS; PLANT EXTRACTS; POLYPHENOLS; SIGNAL TRANSDUCTION;

EID: 84910006077     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2014.08.003     Document Type: Review

References (69)

1. Ravandi F., Talpaz M., Estrov Z. Modulation of cellular signaling pathways: prospects for targeted therapy in hematological malignancies. Clin. Cancer Res 2003, 9:535-550.
2. Zvara A., Hackler L., Nagy Z.B., Micsik T., Puskas L.G. New molecular methods for classification, diagnosis and therapy prediction of hematological malignancies. Pathol. Oncol. Res 2002, 8:231-240.
3. Shi M., Xiao R., Woda B.A., Yu H. Five important advances in hematopathology. Arch. Pathol. Lab. Med 2014, 138:410-419.
4. Solary E., Droin N., Bettaieb A., Corcos L., Dimanche-Boitrel M.T., Garrido C. Positive and negative regulation of apoptotic pathways by cytotoxic agents in hematological malignancies. Leukemia 2000, 14:1833-1849.
5. Experts in Chronic Myeloid Leukemia The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood 2013, 121:4439-4442.
6. Koehn F.E., Carter G.T. The evolving role of natural products in drug discovery. Nat. Rev. Drug Discov 2005, 4:206-220.
7. Cragg G.M., Grothaus P.G., Newman D.J. Impact of natural products on developing new anti-cancer agents. Chem. Rev 2009, 109:3012-3043.
8. Graham J.G., Quinn M.L., Fabricant D.S., Farnsworth N.R. Plants used against cancer - an extension of the work of Jonathan Hartwell. J. Ethnopharmacol 2000, 73:347-377.
9. Chen A.Y., Chen Y.C. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem 2013, 138:2099-2107.
10. Romano B., Pagano E., Montanaro V., Fortunato A.L., Milic N., Borrelli F. Novel insights into the pharmacology of flavonoids. Phytother. Res 2013, 27:1588-1596.
11. Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem. Pharmacol 1983, 32:1141-1148.
12. Chen H., Mrazek A.A., Wang X., Ding C., Ding Y., Porro L.J., et al. Design, synthesis, and characterization of novel apigenin analogues that suppress pancreatic stellate cell proliferation in vitro and associated pancreatic fibrosis in vivo. Bioorg. Med. Chem 2014, 22:3393-3404.
13. Ren W., Qiao Z., Wang H., Zhu L., Zhang L. Flavonoids: promising anticancer agents. Med. Res. Rev 2003, 23:519-534.
14. Zhang X.W., Li W.F., Li W.W., Ren K.H., Fan C.M., Chen Y.Y., et al. Protective effects of the aqueous extract of Scutellaria baicalensis against acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells. Pharm. Biol 2011, 49:256-261.
15. Gasiorowski K., Lamer-Zarawska E., Leszek J., Parvathaneni K., Yendluri B.B., Blach-Olszewska Z., et al. Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration?. CNS Neurol. Disord. Drug Targets 2011, 10:184-191.
16. Li-Weber M. New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents wogonin, baicalein and baicalin. Cancer Treat. Rev 2009, 35:57-68.
17. 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, 31:523-530.
18. Wu H., Long X., Yuan F., Chen L., Pan S., Liu Y., et al. Combined use of phospholipid complexes and self-emulsifying microemulsions for improving the oral absorption of a BCS class IV compound, baicalin. Acta Pharm. Sin. B 2014, 4:217-226.
19. Zhang L., Lin G., Zuo Z. Involvement of UDP-glucuronosyltransferases in the extensive liver and intestinal first-pass metabolism of flavonoid baicalein. Pharm. Res 2007, 24:81-89.
20. Zhang Y., Luo R., Chen Y., Ke X., Hu D., Han M. Application of carrier and plasticizer to improve the dissolution and bioavailability of poorly water-soluble baicalein by hot melt extrusion. AAPS PharmSciTech 2014, 15:560-568.
21. Xing J., Chen X., Zhong D. Absorption and enterohepatic circulation of baicalin in rats. Life Sci 2005, 78:140-146.
22. Lai M.Y., Hsiu S.L., Tsai S.Y., Hou Y.C., Chao P.D. Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats. J. Pharm. Pharmacol 2003, 55:205-209.
23. Akao T., Kawabata K., Yanagisawa E., Ishihara K., Mizuhara Y., Wakui Y., et al. Baicalin, the predominant flavone glucuronide of Scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J. Pharm. Pharmacol 2000, 52:1563-1568.
24. Taiming L., Xuehua J. Investigation of the absorption mechanisms of baicalin and baicalein in rats. J. Pharm. Sci 2006, 95:1326-1333.
25. Zhang L., Li C., Lin G., Krajcsi P., Zuo Z. Hepatic metabolism and disposition of baicalein via the coupling of conjugation enzymes and transporters-in vitro and in vivo evidences. AAPS J. 2011, 13:378-389.
26. Zhang L., Lin G., Chang Q., Zuo Z. Role of intestinal first-pass metabolism of baicalein in its absorption process. Pharm. Res 2005, 22:1050-1058.
27. Zhang J., Lv H., Jiang K., Gao Y. Enhanced bioavailability after oral and pulmonary administration of baicalein nanocrystal. Int. J. Pharm 2011, 420:180-188.
28. Liu J., Qiu L., Gao J., Jin Y. Preparation, characterization and in vivo evaluation of formulation of baicalein with hydroxypropyl-beta-cyclodextrin. Int. J. Pharm 2006, 312:137-143.
29. Liu W., Tian R., Hu W., Jia Y., Jiang H., Zhang J., et al. Preparation and evaluation of self-microemulsifying drug delivery system of baicalein. Fitoterapia 2012, 83:1532-1539.
30. He X., Pei L., Tong H.H., Zheng Y. Comparison of spray freeze drying and the solvent evaporation method for preparing solid dispersions of baicalein with Pluronic F68 to improve dissolution and oral bioavailability. AAPS PharmSciTech 2011, 12:104-113.
31. Yue P.F., Li Y., Wan J., Wang Y., Yang M., Zhu W.F., et al. Process optimization and evaluation of novel baicalin solid nanocrystals. Int. J. Nanomedicine 2013, 8:2961-2973.
32. Zhao L., Wei Y., Huang Y., He B., Zhou Y., Fu J. Nanoemulsion improves the oral bioavailability of baicalin in rats: in vitro and in vivo evaluation. Int. J. Nanomedicine 2013, 8:3769-3779.
33. Hao J., Wang F., Wang X., Zhang D., Bi Y., Gao Y., et al. Development and optimization of baicalin-loaded solid lipid nanoparticles prepared by coacervation method using central composite design. Eur. J. Pharm. Sci 2012, 47:497-505.
34. De Martino L., Arena G.D., Filosa R., Peduto A., Zeppa R., De Feo V. Natural compounds in anti-leukaemic therapy: a review. Mini Rev. Med. Chem 2011, 11:492-502.
35. Himeji M., Ohtsuki T., Fukazawa H., Tanaka M., Yazaki S., Ui S., et al. Difference of growth-inhibitory effect of Scutellaria baicalensis-producing flavonoid wogonin among human cancer cells and normal diploid cell. Cancer Lett 2007, 245:269-274.
36. Huang S.T., Wang C.Y., Yang R.C., Chu C.J., Wu H.T., Pang J.H. Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells. Phytomedicine 2010, 17:47-54.
37. Ozmen A., Madlener S., Bauer S., Krasteva S., Vonach C., Giessrigl B., et al. In vitro anti-leukemic activity of the ethno-pharmacological plant Scutellaria orientalis ssp. carica endemic to western Turkey. Phytomedicine 2010, 17:55-62.
38. Ikezoe T., Chen S.S., Heber D., Taguchi H., Koeffler H.P. Baicalin is a major component of PC-SPES which inhibits the proliferation of human cancer cells via apoptosis and cell cycle arrest. Prostate 2001, 49:285-292.
39. Chen Z.T., Dong Q., Zhang L. [Study on effect of qingkailing injection and its active principle in inducing cell apoptosis in human acute promyelocytic leukemia]. Zhongguo Zhong Xi Yi Jie He Za Zhi 2001, 21:840-842.
40. Ciesielska E., Gwardys A., Metodiewa D. Anticancer, antiradical and antioxidative actions of novel Antoksyd S and its major components, baicalin and baicalein. Anticancer Res 2002, 22:2885-2891.
41. Ciesielska E., Wolszczak M., Gulanowski B., Szulawska A., Kochman A., Metodiewa D. In vitro antileukemic, antioxidant and prooxidant activities of Antoksyd S (C/E/XXI): a comparison with baicalin and baicalein. In Vivo 2004, 18:497-503.
42. Romanouskaya T.V., Grinev V.V. Cytotoxic effect of flavonoids on leukemia cells and normal cells of human blood. Bull. Exp. Biol. Med 2009, 148:57-59.
43. Dong Q.H., Zheng S., Xu R.Z., Lu Q.H. [Baicalein selectively induce apoptosis in human leukemia K562 cells]. Yao Xue Xue Bao 2003, 38:817-820.
44. Wang A.M., Ku H.H., Liang Y.C., Chen Y.C., Hwu Y.M., Yeh T.S. The autonomous notch signal pathway is activated by baicalin and baicalein but is suppressed by niclosamide in K562 cells. J. Cell. Biochem 2009, 106:682-692.
45. Huang H.C., Hsieh L.M., Chen H.W., Lin Y.S., Chen J.S. Effects of baicalein and esculetin on transduction signals and growth factors expression in T-lymphoid leukemia cells. Eur. J. Pharmacol 1994, 268:73-78.
46. Lin X.C., Liu X.G., Chen X.W., Chen W.Z., Liang N.C. [Inhibitory effect and its kinetic analysis of baicalein on recombinant human protein kinase CK2 holoenzyme]. Ai Zheng 2004, 23:874-878.
47. Shieh D.E., Cheng H.Y., Yen M.H., Chiang L.C., Lin C.C. Baicalin-induced apoptosis is mediated by Bcl-2-dependent, but not p53-dependent, pathway in human leukemia cell lines. Am. J. Chin. Med 2006, 34:245-261.
48. Chen Y.J., Wu C.S., Shieh J.J., Wu J.H., Chen H.Y., Chung T.W., et al. Baicalein triggers mitochondria-mediated apoptosis and enhances the antileukemic effect of vincristine in childhood acute lymphoblastic leukemia CCRF-CEM cells. Evid. Based Complement. Alternat. Med 2013, 2013:124747.
49. Li Y.C., Tyan Y.S., Kuo H.M., Chang W.C., Hsia T.C., Chung J.G. Baicalein induced in vitro apoptosis undergo caspases activity in human promyelocytic leukemia HL-60 cells. Food Chem. Toxicol 2004, 42:37-43.
50. Li Y.C., Tyan Y.S., Lee Y.M., Tsao T.Y., Chuang J.Y., Kuo H.M., et al. N-Acetyltransferase is involved in baicalein-induced N-acetylation of 2-aminofluorene and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells. In Vivo 2005, 19:399-405.
51. Wang J., Yu Y., Hashimoto F., Sakata Y., Fujii M., Hou D.X. Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells. Int. J. Mol. Med 2004, 14:627-632.
52. Chow J.M., Shen S.C., Wu C.Y., Chen Y.C. 12-o-Tetradecanoylphorbol 13-acetate prevents baicalein-induced apoptosis via activation of protein kinase C and JNKs in human leukemia cells. Apoptosis 2006, 11:1999-2011.
53. Zheng J., Hu J.D., Chen Y.Y., Chen B.Y., Huang Y., Zheng Z.H., et al. Baicalin induces apoptosis in leukemia HL-60/ADR cells via possible down-regulation of the PI3K/Akt signaling pathway. Asian Pac. J. Cancer Prev 2012, 13:1119-1124.
54. Shih Y.T., Wu D.C., Liu C.M., Yang Y.C., Chen I.J., Lo Y.C. San-Huang-Xie-Xin-Tang inhibits Helicobacter pylori-induced inflammation in human gastric epithelial AGS cells. J. Ethnopharmacol 2007, 112:537-544.
55. Salini S., Chubicka T., Sasidharan N., Sindhu E.R., Babu T.D. Cytotoxic and antioxidant properties of selected Scutellaria species from the Western Ghats of Peninsular India. Pharm. Biol 2013, 51:152-159.
56. Huang Y., Hu J., Zheng J., Li J., Wei T., Zheng Z., et al. Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin. J. Exp. Clin. Cancer Res 2012, 31:48.
57. Castelli R., Gualtierotti R., Orofino N., Losurdo A., Gandolfi S., Cugno M. Current and emerging treatment options for patients with relapsed myeloma. Clin. Med. Insights. Oncol 2013, 7:209-219.
58. 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, 105:3312-3318.
59. Lin M.G., Liu L.P., Li C.Y., Zhang M., Chen Y., Qin J., et al. Scutellaria extract decreases the proportion of side population cells in a myeloma cell line by down-regulating the expression of ABCG2 protein. Asian Pac. J. Cancer Prev 2013, 14:7179-7186.
60. Gu Y.Y., Liu L.P., Qin J., Zhang M., Chen Y., Wang D., et al. Baicalein decreases side population proportion via inhibition of ABCG2 in multiple myeloma cell line RPMI 8226 in vitro. Fitoterapia 2014, 94:21-28.
61. Li Q.B., You Y., Chen Z.C., Lu J., Shao J., Zou P. Role of Baicalein in the regulation of proliferation and apoptosis in human myeloma RPMI8226 cells. Chin. Med. J. (Engl.) 2006, 119:948-952.
62. Liu S., Ma Z., Cai H., Li Q., Rong W., Kawano M. Inhibitory effect of baicalein on IL-6-mediated signaling cascades in human myeloma cells. Eur. J. Haematol 2010, 84:137-144.
63. Xu C.P., Cai H.L., He L., Ma Z., Liu S.Q. [Effect of baicalein on proliferation and migration in multiple myeloma cell lines RPMI 8226 and U266 cells]. Zhonghua Xue Ye Xue Za Zhi 2012, 33:938-943.
64. Ren X., Zhang Y., Li C., Wang H., Jiang Z., Zhang Z., et al. Enhancement of baicalin by hexamethylene bisacetamide on the induction of apoptosis contributes to simultaneous activation of the intrinsic and extrinsic apoptotic pathways in human leukemia cells. Oncol. Rep 2013, 30:2071-2080.
65. Otsuyama K.I., Ma Z., Abroun S., Amin J., Shamsasenjan K., Asaoku H., et al. PPARbeta-mediated growth suppression of baicalein and dexamethasone in human myeloma cells. Leukemia 2007, 21:187-190.
66. Zhang R.B., He L., Huang Z., Ma Z., Liu S.Q. [Synergistic effect and mechanism of baicalein in combination with lenalidomide-induced apoptosis of myeloma cells]. Zhonghua Xue Ye Xue Za Zhi 2013, 34:546-547.
67. Ding D., Zhang B., Meng T., Ma Y., Wang X., Peng H., et al. Novel synthetic baicalein derivatives caused apoptosis and activated AMP-activated protein kinase in human tumor cells. Org. Biomol. Chem 2011, 9:7287-7291.
68. Donald G., Hertzer K., Eibl G. Baicalein - an intriguing therapeutic phytochemical in pancreatic cancer. Curr. Drug Targets 2012, 13:1772-1776.
69. Luo R., Wang J., Zhao L., Lu N., You Q., Guo Q., et al. Synthesis and biological evaluation of baicalein derivatives as potent antitumor agents. Bioorg. Med. Chem. Lett 2014, 24:1334-1338.