Duchesnea Phenolic Fraction Inhibits Tumor Growth through Restoring the Th1/Th2 Balance in U14 Cervical Cancer Bearing Mice

Bo Peng, Qin Hu, Lihua Sun, Xinmin Liu, Jianrong Li, Qi Chang, Liwei Wang, Jintian Tang

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
Institute of Medicinal Physics & Engineering, Tsinghua University, Beijing, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences,Peking Union Medical College, Beijing, China.

DOI: 10.4236/cm.2012.31007                

Abstract

Duchesnea indica (Andr.) Focke has been traditionally used to treat cancer in Asian countries for centuries. In the present study, transplanted U14 cervical cancer mouse model was used to evaluate the antitumor and immunomodulatory activity of Duchesnea phenolic fraction (DPF). ELISA and RIA assay were employed to measured the serum concentration of Th1/Th2 cytokines (IL-2, IL-4, IFN-γ and TNF-α). Administration with 0.25 g/kg, 0.5 g/kg and 1 g/kg DPF significantly reduced the tumor weight by 34.37%, 43.89% and 56.28%, respectively, as compared to the tumor control group. Furthermore, the serum level of IL-2, IFN-γ and TNF-α increased and IL-4 level decreased in a dose-dependent manner during DPF treatment, indicating that the antitumor activity of DPF may be associated with the decrease of TNF-α level and restoration of the balance of Th1/Th2 cell responses. These data suggested that DPF, a mixture of plant polyphenols, had potent anticancer activity which was in part accomplished by its immunomodulatory ability.

Keywords

Duchesnea indica (Andr.) Focke; Cervical Cancer; Th1/Th2 Cell Responses

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	R. W. Melvold and R. P. Sticca, “Basic and Tumor Immunology: A Review,” Surgical Oncology Clinics of North America, Vol. 16, No. 4, 2007, pp. 711-735. doi:10.1016/j.soc.2007.08.003
[2]	S. Romagnani, “Th1/Th2 Cells,” Inflammatory Bowel Diseases, Vol. 5, No. 4, 1999, pp. 285-294. doi:10.1002/ibd.3780050410
[3]	A. Sharma, M. Rajappa, A. Saxena and M. Sharma, “Cytokine Profile in Indian Women with Cervical Intraepithelial Neoplasia and Cancer Cervix,” International Jour nal of Gynecological Cancer, Vol. 17, No. 4, 2007, pp. 879-885. doi:10.1111/j.1525-1438.2007.00883.x
[4]	N. Nair, S. Mahajan, R. Chawda, C. Kandaswami, T. C. Shanahan and S. A. Schwartz, “Grape Seed Extract Activates Th1 Cells in Vitro,” Clinical and Diagnostic Laboratory Immunology, Vol. 9, No. 2, 2002, pp. 470-476.
[5]	V. E. Ooi and F. Liu, “Immunomodulation and Anti Cancer Activity of Polysaccharide-Protein Complexes,” Current Medicinal Chemistry, Vol. 7, No. 7, 2000, pp. 715-729.
[6]	J. Y. Duan, X. P. Liu and Q. Li, “Research on the Effect of Duchesnea indica (Andr.) Focke,” Pharmacology and Clinics of Chinese Materia Medica, Vol. 14, 1998, p. 28.
[7]	B. Peng, Q. Chang, L. W. Wang, Q. Hu, Y. Q. Wang, J. T. Tang and X. M. Liu, “Suppression of Human Ovarian SKOV-3 Cancer Cell Growth by Duchesnea Phenolic Fraction Is Associated with Cell Cycle Arrest and Apoptosis,” Gynecologic Oncology, Vol. 180, No. 1, 2008, pp. 173-181. doi:10.1016/j.ygyno.2007.09.016
[8]	M. Shoemaker, B. Hamilton, S. H. Dairkee, I. Cohen and M. J. Campbell, “In Vitro Anticancer Activity of Twelve Chinese Medicinal Herbs,” Phytotherapy Research, Vol. 19, No. 7, 2005, pp. 649-651. doi:10.1002/ptr.1702
[9]	B. Peng, Q. Hu, X. M. Liu, L. Wang, Q. Chang, J. Li, J. Tang, N. Wang and Y. Wang, “Duchesnea Phenolic Fraction Inhibits in Vitro and in Vivo Growth of Cervical Cancer through Induction of Apoptosis and Cell Cycle Arrest,” Experimental Biology and Medicine (Maywood), Vol. 234, No. 1, 2009, pp. 74-83. doi:10.3181/0806-RM-204
[10]	B. Peng, Q. Hu, L. W. Wang, Y. Q. Wang, Q. Chang, J. T. Tang, X. M. Liu, Y. Chen and H. X. Dang, “Study on Anticancer Function of Phenolic Extract from Duchesnea Indica and Its Immunological Mechanism,” Chinese Phar macological Bulletin, Vol. 23, No. 8, 2007, pp. 1007-1010.
[11]	R. M. Locksley, N. Killeen and M. J. Lenardo, “The TNF and TNF Receptor Superfamilies: Integrating Mammalian Biology,” Cell, Vol. 104, No. 4, 2001, pp. 487-501. doi:10.1016/S0092-8674(01)00237-9
[12]	R. Horssen, T. L. M. Hagen and A. M. M. Eggermont, “TNF-α in Cancer Treatment: Molecular Insights, Antitumor Effects, and Clinical Utility,” Oncologist, Vol. 11, No. 4, 2006, pp. 397-408. doi:10.1634/theoncologist.11-4-397
[13]	S. Mocellin and D. Nitti, “TNF and Cancer: The Two Sides of the Coin,” Frontiers in Bioscience, Vol. 13, 2008. pp. 2774-2783. doi:10.2741/2884
[14]	R. K. Bhairavabhotla, V. Verma, H. Tongaonkar, S. Shastri, K. Dinshaw and S. Chiplunkar, “Role of IL-10 in Immune Suppression in Cervical Cancer,” Indian Journal of Biochemistry & Biophysics, Vol. 44, No. 5, 2007, pp. 350-356.
[15]	S. Mocellin, F. M. Marincola and H. A. Young, “Interleukin-10 and the Immune Response against Cancer: A Counterpoint,” Journal of Leukocyte Biology, Vol. 78, No. 5, 2005, pp. 1043-1051. doi:10.1189/jlb.0705358