Research Progress of Antitumor Activity by Baicalin and Baicalein

Author(s): Wang Yu, Li Ling

Baicalin and its aglycon, baicalein, are flavonoids present from Scutellaria baicalensis Georgi. Baicalin generally inhibits tumor cells by inducing apoptosis and arresting growth, while baicalein suppresses by regulating autophagy. Certain signaling pathways and regulating factors are involved among the induced-apoptosis and autophagy progress. In suppressing growth, baicalin and baicaein inhibit angiogenesis or induce cell cycle arrest at S phase against proliferation, migration and differentiation. The present agents against tumor still have related side effects. Therefore, the natural and nontoxic flavonoids are promising in present even future tumor treatment.

Antitumor, Baicalin, Baicalein

1. Wang, C. Z., Zhang, C. F., Chen, L., Anderson, S., Lu, F. & Yuan, C. S. (2015) Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin, International journal of oncology. 47, 1749-58.doi:10.3892/ijo.2015.3173
2. Yang Yu, M. P., Ling Li (2015) Baicalin induces apoptosis in hepatic cancer cells in vitro and suppresses tumor growth in vivo, Int J Clin Exp Med. 8, 10
3. Rui, X., Yan, X. I. & Zhang, K. (2016) Baicalein inhibits the migration and invasion of colorectal cancer cells via suppression of the AKT signaling pathway, Oncology letters. 11, 685-688.doi:10.3892/ol.2015.3935
4. Morere, L., Andouard, D., Labrousse, F., Saade, F., Calliste, C. A., Cotin, S., Aubard, Y., Rawlinson, W. D., Esclaire, F., Hantz, S., Ploy, M. C. & Alain, S. (2015) Ex vivo model of congenital cytomegalovirus infection and new combination therapies, Placenta. 36, 41-7.doi:10.1016/j.placenta.2014.11.003
5. Sahu, B. D., Mahesh Kumar, J. & Sistla, R. (2015) Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-kappaB Pathways, PLoS One. 10, e0134139.doi:10.1371/journal.pone.0134139
6. Wang, C. Z., Calway, T. D., Wen, X. D., Smith, J., Yu, C., Wang, Y., Mehendale, S. R. & Yuan, C. S. (2013) Hydrophobic flavonoids from Scutellaria baicalensis induce colorectal cancer cell apoptosis through a mitochondrial-mediated pathway, International journal of oncology. 42, 1018-26.doi:10.3892/ijo.2013.1777
7. Yu, C., Zhang, Z., Zhang, H., Zhen, Z., Calway, T., Wang, Y., Yuan, C. S. & Wang, C. Z. (2013) Pretreatment of baicalin and wogonoside with glycoside hydrolase: a promising approach to enhance anticancer potential, Oncology reports. 30, 2411-8.doi:10.3892/or.2013.2726
8. Shin, H. S., Bae, M. J., Choi, D. W. & Shon, D. H. (2014) Skullcap (Scutellaria baicalensis) extract and its active compound, wogonin, inhibit ovalbumin-induced Th2-mediated response, Molecules. 19, 2536-45.doi:10.3390/molecules19022536
9. Yong Peng, Z.-z. F., Cong-Shan Guo (2015) Effects and Mechanism of Baicalin on Apoptosis of Cervical Cancer HeLa Cells In-vitro, Iranian Journal of Pharmaceutical Research. 14, 12
10. Aryal, P., Kim, K., Park, P. H., Ham, S., Cho, J. & Song, K. (2014) Baicalein induces autophagic cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human cancer cells, The FEBS journal. 281, 4644-58.doi:10.1111/febs.12969
11. Chen, J., Li, Z., Chen, A. Y., Ye, X., Luo, H., Rankin, G. O. & Chen, Y. C. (2013) Inhibitory effect of baicalin and baicalein on ovarian cancer cells, Molecular Sciences. 14, 6012-25.doi:10.3390/ijms14036012
12. Wang, T., Shi, G., Shao, J., Wu, D., Yan, Y., Zhang, M., Cui, Y. & Wang, C. (2015) In vitro antifungal activity of baicalin against Candida albicans biofilms via apoptotic induction, Microbial pathogenesis. 87, 21-9.doi:10.1016/j.micpath.2015.07.006
13. Liao, H. L. & Hu, M. K. (2004) Synthesis and anticancer activities of 5,6,7-trimethylbaicalein derivatives,
14. Zhang, D. Y., Wu J Fau - Ye, F., Ye F Fau - Xue, L., Xue L Fau - Jiang, S., Jiang S Fau - Yi, J., Yi J Fau - Zhang, W., Zhang W Fau - Wei, H., Wei H Fau - Sung, M., Sung M Fau - Wang, W., Wang W Fau - Li, X. & Li, X. (2003) Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis,
15. Choi, E. O., Cho, E. J., Jeong, J. W., Park, C., Hong, S. H., Hwang, H. J., Moon, S. K., Son, C. G., Kim, W. J. & Choi, Y. H. (2016) Baicalein Inhibits the Migration and Invasion of B16F10 Mouse Melanoma Cells through Inactivation of the PI3K/Akt Signaling Pathway, Biomolecules & therapeutics.doi:10.4062/biomolther.2016.094
16. Liu, J. J., Huang, T. S., Cheng, W. F. & Lu, F. J. (2003) Baicalein and baicalin are potent inhibitors of angiogenesis: Inhibition of endothelial cell proliferation, migration and differentiation, International journal of cancer. 106, 559-65.doi:10.1002/ijc.11267
17. Wu, J. Y., Tsai, K. W., Li, Y. Z., Chang, Y. S., Lai, Y. C., Laio, Y. H., Wu, J. D. & Liu, Y. W. (2013) Anti-Bladder-Tumor Effect of Baicalein from Scutellaria baicalensis Georgi and Its Application In Vivo, Evidence-based complementary and alternative medicine : eCAM. 2013, 579751.doi:10.1155/2013/579751
18. LEE, H. Z., LEUNG, H. W. C., LAI, M. Y. & WU, C. H. (2005) Baicalein Induced Cell Cycle Arrest and Apoptosis in Human Lung Squamous Carcinoma CH27 Cells, Anticancer Research. 25, 959-964
19. Zhou, Q. M., Wang, S., Zhang, H., Lu, Y. Y., Wang, X. F., Motoo, Y. & Su, S. B. (2009) The combination of baicalin and baicalein enhances apoptosis via the ERK/p38 MAPK pathway in human breast cancer cells, Acta pharmacologica Sinica. 30, 1648-58.doi:10.1038/aps.2009.166
20. Chen, Y. J., Wu, C. S., Shieh, J. J., Wu, J. H., Chen, H. Y., Chung, T. W., Chen, Y. K. & Lin, C. C. (2013) Baicalein Triggers Mitochondria-Mediated Apoptosis and Enhances the Antileukemic Effect of Vincristine in Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells, Evidence-based complementary and alternative medicine : eCAM. 2013, 124747.doi:10.1155/2013/124747
21. Lee, J. H., Li Yc Fau - Ip, S.-W., Ip Sw Fau - Hsu, S.-C., Hsu Sc Fau - Chang, N.-W., Chang Nw Fau - Tang, N.-Y., Tang Ny Fau - Yu, C.-S., Yu Cs Fau - Chou, S.-T., Chou St Fau - Lin, S.-S., Lin Ss Fau - Lino, C.-C., Lino Cc Fau - Yang, J.-S., Yang Js Fau - Chung, J.-G. & Chung, J. G. The role of Ca2+ in baicalein-induced apoptosis in human breast MDA-MB-231 cancer cells through mitochondria- and caspase-3-dependent pathway,
22. Chen, W.-C., Kuo, T.-H., Tzeng, Y.-S. & Tsai, Y.-C. (2012) Baicalin Induces Apoptosis in SW620 Human Colorectal Carcinoma Cells in Vitro and Suppresses Tumor Growth in Vivo, Molecules. 17, 3844-3857.doi:10.3390/molecules17043844
23. Yi Huang, J. H., , Jing Zheng (2012) Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin, Journal of Experimental & Clinical Cancer Research. 31, 9
24. Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S., Natsume, T., Takehana, K., Yamada, N., Guan, J. L., Oshiro, N. & Mizushima, N. (2009) Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy, Molecular biology of the cell. 20, 1981-91.doi:10.1091/mbc.E08-12-1248
25. Tan, H. Y., Wang, N., Man, K., Tsao, S. W., Che, C. M. & Feng, Y. (2015) Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin, Cell death & disease. 6, e1942.doi:10.1038/cddis.2015.271
26. Peng, X. D., Dai, L. L., Huang, C. Q., He, C. M. & Chen, L. J. (2009) Correlation between anti-fibrotic effect of baicalin and serum cytokines in rat hepatic fibrosis, World journal of gastroenterology. 15, 4720-5.doi:10.3748/wjg.15.4720
27. Ma, Z., Otsuyama K Fau - Liu, S., Liu S Fau - Abroun, S., Abroun S Fau - Ishikawa, H., Ishikawa H Fau - Tsuyama, N., Tsuyama N Fau - Obata, M., Obata M Fau - Li, F.-J., Li Fj Fau - Zheng, X., Zheng X Fau - Maki, Y., Maki Y Fau - Miyamoto, K., Miyamoto K Fau - Kawano, M. M. & Kawano, M. M. 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,
28. Wang, W., Xi, M., Duan, X., Wang, Y. & Kong, F. (2015) Delivery of baicalein and paclitaxel using self-assembled nanoparticles: synergistic antitumor effect in vitro and in vivo, International journal of nanomedicine. 10, 3737-50.doi:10.2147/IJN.S80297