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http://dx.doi.org/10.4062/biomolther.2013.106

Antitumor and Apoptosis Induction Effects of Paeonol on Mice Bearing EMT6 Breast Carcinoma  

Ou, Yetao (Department of Biological Engineering, College of Environment and Chemical Engineering, Yanshan University)
Li, Qingwang (Department of Biological Engineering, College of Environment and Chemical Engineering, Yanshan University)
Wang, Jianjie (College of Basic Medicine, Jiamusi University)
Li, Kun (Department of Biological Engineering, College of Environment and Chemical Engineering, Yanshan University)
Zhou, Shaobo (Department of Life Science, Institute of Biomedical and Environmental Science and Technology, University of Bedfordshire)
Publication Information
Biomolecules & Therapeutics / v.22, no.4, 2014 , pp. 341-346 More about this Journal
Abstract
Paeonol is a major phenolic micromolecular component of Moutan cortex Radicis, a traditional Chinese Medicine. It has shown antitumor effects in previous studies; however, the underlying mechanisms remain unknown. This study investigated the mechanism by giving treatments of placebo, cyclophosphamide, paeonol of 150 and 300 mg/kg to 4 groups of mice bearing EMT6 breast cancer. Apoptosis in tumor cells were confirmed by morphology analysis, including hematoxylin, eosin staining and TUNEL staining. The results showed that the weight of EMT6 breast tumor was significantly reduced in the groups treated with both 150 and 300 mg/kg of paeonol. Immunohistochemical and Western blot results showed that the expression of Bcl-2 was down-regulated while the expression of Bax, caspase 8 and caspase 3 was up-regulated respectively. These results suggest that paeonol exhibits antitumor effects and the mechanism of the inhibition is via induction of apoptosis, regulation of Bcl-2 and Bax expression, and activation of caspase 8 and caspase 3.
Keywords
Apoptosis; Pathway; Breast cancer; Paeonol;
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1 Wang, P. J., Li, Q. W., Li, K., Zhang, X. B., Han, Z. S., Wang, J. J., Gao, D. W. and Li, J. (2012) Betulinic acid exerts immunoregulation and anti-tumor effect on cervical carcinoma (U14) tumor-bearing mice. Pharmazie 67, 733-739.
2 Zhang, H., Gao, M. and Yang, X. (2011) Electrochemical oxidation and detection of paeonol on modified electrode with acetylene black nanoparticles. Colloids Surf B Biointerfaces 87, 378-381.   DOI
3 Mimura, K. and Baba, S. (2001) Determination of paeonol metabolites in man by the use of stable isotopes. Chem. Pharm. Bull. 29, 2043-2050.
4 Mlejnek, P. (2001) Caspase inhibition and N6-benzyladenosine-induced apoptosis in HL-60 cells. J. Cell Biochem. 83, 678-689.   DOI   ScienceOn
5 Ohtsuka, T., Buchsbaum, D., Oliver, P., Makhija, S., Kimberly, R. and Zhou, T. (2003) Synergistic induction of tumor cell apoptosis by death receptor antibody and chemotherapy agent through JNK/p38 and mitochondrial death pathway. Oncogene 22, 2034-2044.   DOI   ScienceOn
6 Pan, X. D., Fei, Q. Z., Zhu, C. G. and Liang, B. (2004) Synthesis of five paeonol esters and their activity in vitro and in vivo anti-tumor. Anhui Medical and Pharmaceutical Journal 8, 16-18.
7 Reed, J. C. (2000) Mechanisms of apoptosis. Am. J. Pathol. 157, 1415-1430.   DOI   ScienceOn
8 Sjostrom, J., Blomqvist, C., von Boguslawski, K., Bengtsson, N. O., Mjaaland, I., Malmstrom, P., Ostenstadt, B., Wist, E., Valvere, V., Takayama, S., Reed, J. C. and Saksela, E. (2002) The predictive value of Bcl-2, Bax, Bcl-xL, bag-1, fas and fasL for chemotherapy response in advanced breast cancer. Clin. Cancer Res. 8, 811-816.
9 Sun, G. P., Wan, X., Xu, S. P., Wang, H., Liu, S. H. and Wang, Z. G. (2008) Antiproliferation and apoptosis induction of paeonol in human esophageal cancer cell lines. Dis. Esophagus 21, 723-729.   DOI   ScienceOn
10 Sun, G. P., Wang, H., Xu, S. P., Wu, Q., Chen, Z. D. and Wei, W. (2008) Anti-tumor effects of paeonol in a HepA- hepatoma bearing mouse model via induction of tumor cell apoptosis and stimulation of IL-2 and TNF-$\alpha$ production. Eur. J. Pharmacol. 584, 246-252.   DOI
11 Xing, G., Zhang, Z., Liu, J., Hu, H. and Sugiura, N. (2010) Antitumor effect of extracts from moutan cortex on DLD-1 human colon cancer cells in vitro. Mol. Med. Report. 3, 57-61.
12 Chou, T. C. (2003) Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia. Br. J. Pharmacol. 139, 1146-1152.   DOI   ScienceOn
13 Wan, X. A., Sun, G. P., Wang, H., Xu, S. P., Wang, Z. G. and Liu, S. H. (2008) Synergistic effect of paeonol and cisplatin on oesophageal cancer cell lines. Dig. Liver Dis. 40, 531-539.   DOI   ScienceOn
14 Wang, J. J., Li, Q. W., Ou, Y. T., Li, C. J., Sun, X. X. and Tian, Y. Z. (2010) Antitumor effects of paeonol on mice bearing EMT6 breast infiltrating ductal carcinoma. Lat. Am. J. Pharm. 5, 369-375.
15 Cheung, T. H., Chung, T. K., Lo, K. W., Yu, M. Y., Krajewski, S., Reed, J. C. and Wong, Y. F. (2002) Apotosis-related proteins in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix. Gynecol. Oncol. 86, 14-18.   DOI   ScienceOn
16 Dai, M., Liu, Q. Y., Gu, C. G. and Zhang, H. Y. (2000) Inhibitory effect of paeonol on lipid peroxidational reaction and oxidational decorate of low density lipoprotein. Zhongguo Zhong Yao Za Zhi 25, 625-627.
17 Li, K., Li, Q. W., Zhang, T., Han, Z. S., Li, J., Liu, Z. W. and Zheng, F. L. (2011) Procyanidins from Pinus koraiensis bark inhibits HeLa cell growth by inducing apoptosis and reducing survivin protein expression. Afr. J. Biotechnol. 40, 7766-7771.
18 Li, N., Fan, L. L., Sun, G. P., Wan, X. A., Wang, Z. G., Wu, Q. and Wang, H. (2010) Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo. World J. Gastroenterol. 16, 4483-4490.   DOI
19 Sun, Y. C., Shen, Y. X., and Sun, G. P. (2004) Advances in the studies of major pharmacological activity of paeonol. Chin. Chin. Tradit. Pat. Med. 26, 579-582.
20 Zhang, T., Li, Q. W., Li, K., Li, Y. R., Li, J., Wang, G. J. and Zhou, S. B. (2008) Antitumor effects of saponin extract from Patrinia villosa juss on mice bearing U14 cervical cancer. Phytother Res. 22, 640-645.   DOI   ScienceOn
21 Liu, C. Q., Tan, S. Y., Ji, C. Y., Luo, H. S. and Yu, J. P. (2005) The effects of paeonol on inhibiting the proliferation of human colorectal cancer cell lines HT-29 and its molecular mechanism. Chin. Pharm. Bull. 21, 1251-1254.