Ginsenoside Rh2 suppresses growth of uterine leiomyoma in vitro and in vivo and may regulate ERα/c-Src/p38 MAPK activity

Journal of Functional Foods

Volumn 18, Issue , 2015, Pages 73-82

  Zhu, Yan ^a,b   Xu, Junjiu ^c   Li, Zhao ^a,b   Xie, Shuwu ^a,b   Zhou, Jieyun ^a,b   Guo, Xiangjie ^a,b   Zhou, Xianying ^a,b   Li, Guoting ^a   Zhong, Ruihua ^a   Ma, Aying ^a,d  

^a SHANGHAI INSTITUTE OF PLANNED PARENTHOOD RESEARCH   (China)

^b Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices   (China)

^c SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^d FUDAN UNIVERSITY   (China)

Author keywords

C Src; ER ; Ginsenoside Rh2; P38 MAPK; Uterine leiomyoma

Indexed keywords

EID: 84942512021     PISSN: 17564646     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jff.2015.06.057     Document Type: Article

References (31)

1. Campbell R.A., Bhat-Nakshatri P., Patel N.M., Constantinidou D., Ali S., Nakshatri H. Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: A new model for anti-estrogen resistance. The Journal of Biological Chemistry 2001, 276(13):9817-9824.
2. Chang T.L., Huang Y.H., Ou Y.D. The role of ginsenosides in inhibiting ubiquitin activating enzyme (E1) activity. Journal of Functional Foods 2014, 7:462-470.
3. Chu I., Arnaout A., Loiseau S., Sun J., Seth A., McMahon C., Chun K., Hennessy B., Mills G.B., Nawaz Z., Slingerland J.M. Src promotes estrogen-dependent estrogen receptor alpha proteolysis in human breast cancer. The Journal of Clinical Investigation 2007, 117(8):2205-2215.
4. Cramer S.F., Patel A. The frequency of uterine leiomyomas. American Journal of Clinical Pathology 1990, 94(4):435-438.
5. Donnez J., Tomaszewsk J., Vázquez F., Bouchard P., Lemieszczuk B., Baró F., Nouri K., Selvaggi L., Sodowski K., Bestel E., Terrill P., Osterloh I., Loumaye E. Ulipristal acetate versus leuprolide acetate for uterine fibroids. The New England Journal of Medicine 2012, 366(5):421-432. PEARL II Study Group.
6. Edwards D.P., Boonyaratanakornkit V. Rapid extranuclear signaling by the estrogen receptor (ER): MNAR couples ER and Src to the MAP kinase signaling pathway. Molecular Interventions 2003, 3(1):12-15.
7. Everitt J.I., Wolf D.C., Howe S.R., Goldsworthy T.L., Walker C. Rodent model of reproductive tract leiomyoma. Clinical and pathological features. American Journal of Pathology 1995, 146(6):1556-1567.
8. Fujii S., Nakashima N., Okamura H., Takenaka A., Kanzaki H., Okuda Y., Morimoto K., Nishimura T. Progesterone-induced smooth muscle-like cells in the subperitoneal nodules produced by estrogen. Experimental approach to leiomyomatosis peritonealis disseminata. American Journal of Obstetrics and Gynecology 1981, 139(2):164-172.
9. Fujisawa T., Velichko S., Thai P., Hung L.Y., Wu R. Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-κB paradigm. The Journal of Immunology 2009, 183(10):6236-6243.
10. Gu Y., Wang G.J., Sun J.G., Jia Y.W., Wang W., Xu M.J., Lv T., Zheng Y.T., Sai Y. Pharmacokinetic characterization of ginsenoside Rh2, an anticancer nutrient from ginseng, in rats and dogs. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association 2009, 47(9):2257-2268.
11. Guo J.P., Shu S.K., Esposito N.N., Coppola D., Koomen J.M., Cheng J.Q. IKKε phosphorylation of estrogen receptor alpha Ser-167 and contribution to tamoxifen resistance in breast cancer. The Journal of Biological Chemistry 2010, 285(6):3676-3684.
12. Irby R.B., Yeatman T.J. Role of Src expression and activation in human cancer. Oncogene 2000, 19(49):5636-5642.
13. Ishizawar R., Parsons S.J. c-Src and cooperating partners in human cancer. Cancer Cell 2004, 6(3):209-214.
14. Kim M.J., Yun H., Kim D.H., Kang I., Choe W., Kim S.S., Ha J. AMP-activated protein kinase determines apoptotic sensitivity of cancer cells to ginsenoside-Rh2. Journal of Ginseng Research 2014, 38(1):16-21.
15. Lannigan D.A. Estrogen receptor phosphorylation. Steroids 2003, 68(1):1-9.
16. Lee H., Bai W. Regulation of estrogen receptor nuclear export by ligand-induced and p38-mediated receptor phosphorylation. Molecular and Cellular Biology 2002, 22(16):5835-5845.
17. Lee H.Y., Park S.H., Chae S.W., Soung N.K., Oh M.J., Kim J.S., Kim O.Y., Chae H.J. Aqueous ginseng extract has a preventive role in RANKL-induced osteoclast differentiation and estrogen deficiency-induced osteoporosis. Journal of Functional Foods 2015, 13:192-203.
18. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25(4):402-408.
19. Migliaccio A., Castoria G., Di Domenico M., de Falco A., Bilancio A., Lombardi M., Bottero D., Varricchio L., Nanayakkara M., Rotondi A., Auricchio F. Sex steroid hormones act as growth factors. The Journal of Steroid Biochemistry and Molecular Biology 2002, 83(1-5):31-35.
20. Migliaccio A., Castoria G., Di Domenico M., De Falco A., Bilancio A., Auricchio F. Src is an initial target of sex steroid hormone action. Annals of the New York Academy of Sciences 2002, 963:185-190.
21. Shi J., Cao B., Zha W.B., Wu X.L., Liu L.S., Xiao W.J., Gu R.R., Sun R.B., Yu X.Y., Zheng T., Li M.J., Wang X.W., Zhou J., Mao Y., Ge C., Ma T., Xia W.J., Aa J.Y., Wang G.J., Liu C.X. Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo. Acta Pharmacologica Sinica 2013, 34(10):1349-1358.
22. Walker C.L., Hunter D., Everitt J.I. Uterine leiomyoma in the Eker rat: A unique model for important diseases of women. Genes, Chromosomes and Cancer 2003, 38(4):349-356.
23. Walker C.L., Stewart E.A. Uterine fibroids: The elephant in the room. Science 2005, 308(5728):1589-1592.
24. Wang G., Ishikawa H., Sone K., Kobayashi T., Kim J.J., Kurita T., Shozu M. Nonobese diabetic/severe combined immunodeficient murine xenograft model for human uterine leiomyoma. Fertility and Sterility 2014, 101(5):1485-1492.
25. Weihua Z., Ekman J., Almkvist A., Saji S., Wang L., Warner M., Gustafsson J.A. Involvement of androgen receptor in 17-beta-estradiol-induced cell proliferation in rat uterus. Biology of Reproduction 2002, 67(2):616-623.
26. Yue P.Y., Mak N.K., Cheng Y.K., Leung K.W., Fan D.T., Yeung H.W., Wong R.N. Pharmacogenomics and the Yin/Yang actions of ginseng: Anti-tumor, angiomodulating and steroid-like activities of Ginsenosides. Chinese Medicine 2007, 2:6.
27. Zhang D., Trudeau V.L. Integration of membrane and nuclear estrogen receptor signaling. Comparative Biochemistry and Physiology. Part A, Molecular and Integrative Physiology 2006, 144(3):306-315.
28. Zhao H.X., Zhao Y.Z., Yin L.J. Survey of women's diseases 2001~2004. Maternal and Child Health Care of China 2005, 20:1435-1436.
29. Zhu Y., Qiu X.Y., Wang L., Wu J.H., Liu G.M., He G.L., Jiang X.R., Sun Z.Y., Cao L. Effects of gestrinone on uterine leiomyoma and expression of c-Src in a guinea pig model. Acta Pharmacologica Sinica 2007, 28(5):685-694.
30. Zhu Y., Xie S.W., Zhang J.F., Zhang T.T., Zhou J.Y., Cao Y., Cao L. Involvement of Bcl-2, Src, and ERα in gossypol-mediated growth inhibition and apoptosis in human uterine leiomyoma and myometrial cells. Acta Pharmacologica Sinica 2010, 31(12):1593-1603.
31. Zhu Y., Zhang T.T., Xie S.W., Tu R.Q., Cao Y., Guo X.J., Zhou J.Y., Zhou X.Y., Cao L. Gestrinone inhibits growth of human uterine leiomyoma may relate to activity regulation of ERα, Src and P38 MAPK. Biomedicine and Pharmacotherapy 2012, 66(8):569-577.