Ursolic acid induces apoptosis in human leukaemia cells and exhibits anti-leukaemic activity in nude mice through the PKB pathway

British Journal of Pharmacology

Volumn 165, Issue 6, 2012, Pages 1813-1826

  Gao, Ning ^a,b   Cheng, Senping ^b   Budhraja, Amit ^b   Gao, Ziyi ^b   Chen, Jieping ^a   Liu, E Hu ^a   Huang, Cheng ^b   Chen, Deying ^a   Yang, Zailin ^a   Liu, Qun ^c   Li, Ping ^c   Shi, Xianglin ^b   Zhang, Zhuo ^b  

^a CHONGQING MEDICAL UNIVERSITY   (China)

^b UNIVERSITY OF KENTUCKY   (United States)

^c CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

apoptosis; leukaemia; PKB; ursolic acid; xenograft

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; CASPASE; PLACEBO; PROTEIN KINASE B; PROTEIN MCL 1; SMALL INTERFERING RNA; STRESS ACTIVATED PROTEIN KINASE; URSOLIC ACID;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DOWN REGULATION; DRUG FATALITY; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; EXPERIMENTAL MOUSE; HUMAN; HUMAN CELL; IN VIVO STUDY; LEUKEMIA; LEUKEMIA CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT;

EID: 84863127744     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01684.x     Document Type: Article

References (49)

1. Abe F, Yamauchi T, Nagao T, Kinjo J, Okabe H, Higo H, et al,. (2002). Ursolic acid as a trypanocidal constituent in rosemary. Biol Pharm Bull 25: 1485-1487.
2. Araki T, Hayashi M, Watanabe N, Kanuka H, Yoshino J, Miura M, et al,. (2002). Down regulation of Mcl-1 by inhibition of the PI3-K/Akt pathway is required for cell shrinkage-dependent cell death. Biochem Biophys Res Commun 290: 1275-1281.
3. 2+ release mediates ursolic acid-induced apoptosis in human leukemic HL-60 cells. Int J Cancer 73: 725-728.
4. Blanco-Aparicio C, Renner O, Leal JF, Carnero A, (2007). PTEN, more than the AKT pathway. Carcinogenesis 28: 1379-1386.
5. Cao J, Danqing X, Wang D, Wu R, Zhang L, Zhu H, et al,. (2009). ROS-driven Akt dephosphorylation at Ser-473 is involved in 4-HPR-mediated apoptosis in NB4 cells. Free Radic Biol Med 47: 536-547.
6. Choi YH, Baek JH, Yoo MA, Chung HY, Kim ND, Kim KW, (2000). Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells. Int J Oncol 17: 565-571.
7. De Smaele E, Zazzeroni F, Papa S, Nguyen DU, Jin R, Jones J, et al,. (2001). Induction of gadd45β by NF-ΰB downregulates pro-apoptotic JNK signaling. Nature 414: 308-313.
8. Dhanasekaran DN, Reddy EB, (2008). JNK signaling in apoptosis. Oncogene 27: 6245-6251.
9. Donovan N, Becker EB, Konishi Y, Bonni A, (2002). JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. J Biol Chem 277: 40944-40949.
10. Fan M, Chambers TC, (2001). Role of mitogen-activated protein kinases in the response of tumor cells to chemotherapy. Drug Resist Updat 4: 253-267.
11. Franke TF, Kaplan DR, Cantley LC, (1997). PI3K: downstream AKTion blocks apoptosis. Cell 88: 435-437.
12. 2-Terminal kinase. Clin Cancer Res 15: 140-149.
13. Gao T, Furnari F, Newton AC, (2005). PHLPP: a phosphatase that directly dephosphorylates Akt promotes apoptosis and suppresses tumor growth. Mol Cell 18: 13-24.
14. Ikeda Y, Murakami A, Ohigashi H, (2008). Ursolic acid: an anti- and pro-inflammatory triterpenoid. Mol Nutr Food Res 52: 26-42.
15. Inoshita S, Takeda K, Hatai T, Terada Y, Sano M, Hata J, et al,. (2002). Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress. J Biol Chem 277: 43730-43734.
16. Kassi E, Sourlingas TG, Spiliotaki M, Papoutsi Z, Pratsinis H, Aligiannis N, et al,. (2009). Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Invest 27: 723-733.
17. Kim AH, Khursigara G, Sun X, Franke TF, Chao MV, (2001). Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol 21: 893-901.
18. Kim AH, Yano H, Cho H, Meyer D, Monks B, Margolis B, et al,. (2002). Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Neuron 35: 697-709.
19. Kuo ML, Chuang SE, Lin MT, Yang SY, (2001). The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention of apoptosis of Hep3B cells by interleukin-6. Oncogene. 20: 677-685.
20. Lei K, Davis RJ, (2003). JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci U S A 100: 2432-2437.
21. Li Y, Xing D, Chen Q, Chen WR, (2010). Enhancement of chemotherapeutic agent-induced apoptosis by inhibition of NF-ΰB using ursolic acid. Int J Cancer 127: 462-473.
22. Liu TC, Lin PM, Chang JG, Lee JP, Chen TP, Lin SF, (2000). Mutation analysis of PTEN/MMAC1 in acute myeloid leukemia. Am J Hematol 63: 170-175.
23. Liu XS, Jiang J, (2007). Induction of apoptosis and regulation of the MAPK pathway by ursolic acid in human leukemia K562 cells. Planta Med 73: 1192-1194.
24. Maehama T, Dixon JE, (1998). The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3, 4, 5-trisphosphate. J Biol Chem 273: 13375-13378.
25. Manu KA, Kuttan G, (2008). Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-ΰB mediated activation of bcl-2 in B16F-10 melanoma cells. Int Immunopharmacol 8: 974-981.
26. Mao JH, To MD, Perez-Losada J, Wu D, Del Rosario R, Balmain A, (2004). Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression. Genes Dev 18: 1800-1805.
27. Nicholson KM, Anderson NG, (2002). The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 14: 381-395.
28. Ohigashi H, Takamura H, Koshimizu K, Tokuda H, Ito Y, (1986). Inhibitory effects of ursolic and oleanolic ancid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Lett 30: 143-151.
29. Pathak AK, Bhutani M, Nair AS, (2007). Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Mol Cancer Res 5: 943-955.
30. Rinkenberger JL, Horning S, Klocke B, Roth K, Roth K, Korsmeyer SJ, (2000). Unique biology of Mcl-1: therapeutic opportunities in cancer. Genes Dev 14: 23-27.
31. Sato S, Fujita N, Tsuruo T, (2000). Modulation of Akt kinase activity by binding to Hsp90. Proc Natl Acad Sci U S A 97: 10832-10837.
32. Shai LJ, McGaw LJ, Aderogba MA, Mdee LK, Eloff JN, (2008). Four pentacyclic triterpenoids with antifungal and antibacterial activity from Curtisia dentata (Burm.f) C.A. Sm. Leaves. J Ethnopharmacol 119: 238-244.
33. Shan X, Czar MJ, Bunnell SC, Liu P, Liu Y, Schwartzberg PL, et al,. (2000). Deficiency of PTEN in Jurkat T cells causes constitutive localization of Itk to the plasma membrane and hyperresponsiveness to CD3 stimulation. Mol Cell Biol 20: 6945-6957.
34. Shen HM, Liu ZG, (2006). JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med 40: 928-939.
35. Stanbolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, et al,. (1998). Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95: 29-39.
36. 2-terminal kinase activation and cell apoptosis. Mol Cell Biol 24: 1531-1539.
37. Taniguchi S, Imayoshi Y, Kobayashi E, Takamatsu Y, Ito H, Hatano T, et al,. (2002). Production of bioactive triterpenes by Eriobotrya japonica calli. Phytochemistry 59: 315-323.
38. Tu HY, Huang AM, Wei BL, Gan KH, Hour TC, Yang SC, et al,. (2009). Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species. Bioorg Med Chem 17: 7265-7274.
39. Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, et al,. (1996). Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380: 75-79.
40. Vivanco I, Sawyers CL, (2002). The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev 2: 489-501.
41. Wang JM, Chao JR, Chen W, (1999). The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-Kinase/Akt signaling pathway through a transcription factor complex containing CREB. Mol Cell Biol 19: 6195-6206.
42. Wenner CE, (2010). Cell signaling and cancer-possible targets for therapy. J Cell Physiol 223: 299-308.
43. Wilson DJ, Fortner KA, Lynch DH, Mattingly RR, Macara IG, Posada JA, et al,. (1996). JNK, but not MAPK, activation is associated with Fas-mediated apoptosis in human T cells. Eur J Immunol 26: 989-994.
44. Xia Y, Ongusaha P, Lee SW, Liou YC, (2009). Loss of Wip1 sensitizes cells to stress- and DNA damage-induced apoptosis. J Biol Chem 284: 17428-17437.
45. Yang JY, Widmann C, (2002). The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation. J Biol Chem 277: 14641-14646.
46. Yoshida K, Yamaguchi T, Natsume T, Kufe D, Miki Y, (2005). JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage. Nat Cell Biol 7: 278-285.
47. Zanke BW, Boudreau K, Rubie E, Winnett E, Tibbles LA, Zon L, et al,. (1996). The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat. Curr Biol 6: 606-613.
48. Zhang Y, Kong C, Zeng Y, Wang L, Li Z, Wang H, et al,. (2010b). Ursolic acid induces PC3 cell apoptosis via activation of JNK and inhibition of Akt pathways in vitro. Mol Carcinog 49: 374-385.
49. Zhang YX, Kong CZ, Wang LH, Li JY, Liu XK, Xu B, et al,. (2010a). Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation. J Cell Biochem 109: 764-773.