Oridonin, a promising antitumor natural product in the chemotherapy of hematological malignancies

Current Pharmaceutical Biotechnology

Volumn 15, Issue 11, 2014, Pages 1083-1092

  Zhao, Zichu ^a   Chen, Yan ^a  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

Author keywords

Antitumor; Hematological malignancies; Molecular mechanism; Oridonin

Indexed keywords

ABELSON KINASE; ACUTE MYELOID LEUKEMIA 1 EIGHT TWENTY ONE PROTEIN; IMATINIB; MICRORNA; NUCLEOPHOSMIN; ONCOPROTEIN; ORIDONIN; PROMYELOCYTIC LEUKEMIA PROTEIN; PROMYELOCYTIC LEUKEMIA RETINOIC ACID RECEPTOR ALPHA; RETINOID RELATED ORPHAN RECEPTOR ALPHA; TRANSCRIPTION FACTOR RUNX1; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; KAURANE DERIVATIVE;

APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER CHEMOTHERAPY; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHROMOSOME TRANSLOCATION; HEMATOLOGIC MALIGNANCY; HUMAN; NONHUMAN; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; SENSITIVITY ANALYSIS; SIGNAL TRANSDUCTION; CHEMISTRY; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HEMATOLOGIC NEOPLASMS; METABOLISM; PATHOLOGY; TUMOR CELL LINE;

RABDOSIA RUBESCENS;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; CELL LINE, TUMOR; DITERPENES, KAURANE; GENE EXPRESSION REGULATION; HEMATOLOGIC NEOPLASMS; HUMANS; MOLECULAR STRUCTURE;

EID: 84925880439     PISSN: 13892010     EISSN: 18734316     Source Type: Journal    
DOI: 10.2174/1389201015666141111115608     Document Type: Article

References (81)

1. Fouladbakhsh, J.M.; Balneaves, L.; Jenuwine, E. Understanding CAM natural health products: implications of use among cancer patients and survivors. J. Adv. Practitioner Oncol., 2013, 4(5), 289-306.
2. Tan, W.; Lu, J.; Huang, M.; Li, Y.; Chen, M.; Wu, G.; Gong, J.; Zhong, Z.; Xu, Z.; Dang, Y.; Guo, J.; Chen, X.; Wang, Y., Anticancer natural products isolated from chinese medicinal herbs. Chin. Med., 2011, 6(1), 27.
3. Fujita, E.; Nagao, Y.; Node, M.; Kaneko, K.; Nakazawa, S.; Kuroda, H. Antitumor activity of the Isodon diterpenoids: structural requirements for the activity. Experientia, 1976, 32(2), 203-206.
4. Harris, E.S.; Cao, S.; Schoville, S.D.; Dong, C.; Wang, W.; Jian, Z.; Zhao, Z.; Eisenberg, D.M.; Clardy, J. Selection for high oridonin yield in the Chinese medicinal plant Isodon (Lamiaceae) using a combined phylogenetics and population genetics approach. PLoS One, 2012, 7(11), e50753.
5. Zhu, M.; Hong, D.; Bao, Y.; Wang, C.; Pan, W. Oridonin induces the apoptosis of metastatic hepatocellular carcinoma cells via a mitochondrial pathway. Oncol. Lett., 2013, 6(5), 1502-1506.
6. Wang, S.; Zhong, Z.; Wan, J.; Tan, W.; Wu, G.; Chen, M.; Wang, Y. Oridonin induces apoptosis, inhibits migration and invasion on highly-metastatic human breast cancer cells. Amer. J. Chin. Med., 2013, 41(1), 177-196.
7. Cai, D.T.; Jin, H.; Xiong, Q.X.; Liu, W.G.; Gao, Z.G.; Gu, G.X.; Qiu, Y.H. ER stress and ASK1-JNK activation contribute to oridonin-induced apoptosis and growth inhibition in cultured human hepatoblastoma HuH-6 cells. Mol. Cell Biochem., 2013, 379(1-2), 161-169.
8. Li, X.; Li, X.; Wang, J.; Ye, Z.; Li, J.C. Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells. Int. J. Biologic. Sci., 2012, 8(6), 901-912.
9. Liu, Y.; Shi, Q.F.; Qi, M.; Tashiro, S.; Onodera, S.; Ikejima, T. Interruption of hepatocyte growth factor signaling augmented oridonin-induced death in human non-small cell lung cancer A549 cells via c-met-nuclear factor-kappaB-cyclooxygenase-2 and c-Met-Bcl-2-caspase-3 pathways. Biol. Pharm. Bull., 2012, 35(7), 1150-1158.
10. Zhang, Y.H.; Wu, Y.L.; Tashiro, S.; Onodera, S.; Ikejima, T. Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in human cervical carcinoma HeLa cells. Acta Pharmacol. Sin., 2011, 32(10), 1266-1275.
11. Kwan, H.Y.; Yang, Z.; Fong, W.F.; Hu, Y.M.; Yu, Z.L.; Hsiao, W.L. The anticancer effect of oridonin is mediated by fatty acid synthase suppression in human colorectal cancer cells. J. Gastroenterol., 2013, 48(2), 182-192.
12. Chen, G.; Wang, K.; Yang, B.Y.; Tang, B.; Chen, J.X.; Hua, Z.C. Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells. Int. J. Oncol., 2012, 40(1), 139-147.
13. Zhou, G.-B.; Chen, S.-J.; Wang, Z.-Y.; Chen, Z. Back to the future of oridonin: again, compound from medicinal herb shows potent antileukernia efficacies in vitro and in vivo. Cell Research, 2007, 17(4), 274-276.
14. Miyoshi, H.; Kozu, T.; Shimizu, K.; Enomoto, K.; Maseki, N.; Kaneko, Y.; Kamada, N.; Ohki, M. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J., 1993, 12(7), 2715-2721.
15. Peterson, L.F.; Zhang, D.E. The 8; 21 translocation in leukemogenesis. Oncogene, 2004, 23(24), 4255-4262.
16. Gelmetti, V.; Zhang, J.S.; Fanelli, M.; Minucci, S.; Pelicci, P.G.; Lazar, M.A. Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Molecul. Cellular Biol., 1998, 18(12), 7185-7191.
17. Lutterbach, B.; Westendorf, J.J.; Linggi, B.; Patten, A.; Moniwa, M.; Davie, J.R.; Huynh, K.D.; Bardwell, V.J.; Lavinsky, R.M.; Rosenfeld, M.G.; Glass, C.; Seto, E.; Hiebert, S.W. ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Molecul. Cellular Biol., 1998, 18(12), 7176-7184.
18. Frank, R.; Zhang, J.; Uchida, H.; Meyers, S.; Hiebert, S.W.; Nimer, S.D. The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B. Oncogene, 1995, 11(12), 2667-2674.
19. Fenske, T.S.; Pengue, G.; Mathews, V.; Hanson, P.T.; Hamm, S.E.; Riaz, N.; Graubert, T.A. Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice. Proc. Natl. Acad. Sci. USA, 2004, 101(42), 15184-15189.
20. Okuda, T.; Cai, Z.L.; Yang, S.L.; Lenny, N.; Lyu, C.J.; van Deursen, J.M.A.; Harada, H.; Downing, J.R. Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. Blood, 1998, 91(9), 3134-3143.
21. Burel, S.A.; Harakawa, N.; Zhou, L.M.; Pabst, T.; Tenen, D.G.; Zhang, D.E. Dichotomy of AML1-ETO functions: Growth arrest versus block of differentiation. Molecul. Cellular Biol., 2001, 21(16), 5577-5590.
22. Pabst, T.; Mueller, B.U.; Harakawa, N.; Schoch, C.; Haferlach, T.; Behre, G.; Hiddemann, W.; Zhang, D.E.; Tenen, D.G. AML1-ETO downregulates the granulocytic differentiation factor C/EBP alpha in t(8;21) myeloid leukemia. Nat. Med., 2001, 7(4), 444-451.
23. Elagib, K.E.; Goldfarb, A.N. Oncogenic pathways of AML1-ETO in acute myeloid leukemia: Multifaceted manipulation of marrow maturation. Cancer Letters, 2007, 251(2), 179-186.
24. Zhou, G.-B.; Kang, H.; Wang, L.; Gao, L.; Liu, P.; Xie, J.; Zhang, F.-X.; Weng, X.-Q.; Shen, Z.-X.; Chen, J.; Gu, L.-J.; Yan, M.; Zhang, D.-E.; Chen, S.-J.; Wang, Z.-Y.; Chen, Z. Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo. Blood, 2007, 109(8), 3441-3450.
25. Zhen, T.; Wu, C.-F.; Liu, P.; Wu, H.-Y.; Zhou, G.-B.; Lu, Y.; Liu, J.-X.; Liang, Y.; Li, K.K.; Wang, Y.-Y.; Xie, Y.-Y.; He, M.-M.; Cao, H.-M.; Zhang, W.-N.; Chen, L.-M.; Petrie, K.; Chen, S.-J.; Chen, Z. Targeting of AML1-ETO in t(8;21) leukemia by oridonin generates a tumor suppressor-like protein. Sci. Translat. Med., 2012, 4(127).
26. Wu, C.; Zhen, T.; Zhou, G.; Liu, P.; Chen, Z.; Chen, S. Oridoningenerated cleavage fragment of AML1-ETO inhibits its oligomerization and oncogenic function leading to differentiation and apoptosis of leukemic cells. Blood, 2009, 114(22), 435-435.
27. Falini, B.; Mecucci, C.; Tiacci, E.; Alcalay, M.; Rosati, R.; Pasqualucci, L.; La Starza, R.; Diverio, D.; Colombo, E.; Santucci, A.; Bigerna, B.; Pacini, R.; Pucciarini, A.; Liso, A.; Vignetti, M.; Fazi, P.; Meani, N.; Pettirossi, V.; Saglio, G.; Mandelli, F.; Lo-Coco, F.; Pelicci, P.G.; Martelli, M.F. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N. Engl. J. Med., 2005, 352(3), 254-266.
28. Falini, B.; Gionfriddo, I.; Cecchetti, F.; Ballanti, S.; Pettirossi, V.; Martelli, M.P. Acute myeloid leukemia with mutated nucleophosmin (NPM1): any hope for a targeted therapy? Blood Rev., 2011, 25(6), 247-254.
29. Falini, B.; Martelli, M.P.; Bolli, N.; Sportoletti, P.; Liso, A.; Tiacci, E.; Haferlach, T. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood, 2011, 117(4), 1109-1120.
30. Leong, S.M.; Tan, B.X.; Bte, A.B.; Yan, T.; Chee, L.Y.; Ang, S.T.; Tay, K.G.; Koh, L.P.; Yeoh, A.E.; Koay, E.S.; Mok, Y.K.; Lim, T.M. Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and-8 inhibition. Blood, 2010, 116(17), 3286-3296.
31. Falini, B.; Bolli, N.; Shan, J.; Martelli, M.P.; Liso, A.; Pucciarini, A.; Bigerna, B.; Pasqualucci, L.; Mannucci, R.; Rosati, R.; Gorello, P.; Diverio, D.; Roti, G.; Tiacci, E.; Cazzaniga, G.; Biondi, A.; Schnittger, S.; Haferlach, T.; Hiddemann, W.; Martelli, M.F.; Gu, W.; Mecucci, C.; Nicoletti, I., Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML. Blood, 2006, 107(11), 4514-4523.
32. Li, F.F.; Yi, S.; Wen, L.; He, J.; Yang, L.J.; Zhao, J.; Zhang, B.P.; Cui, G.H.; Chen, Y., Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+ acute myeloid leukemia cells in vitro. Acta Pharmacol. Sin., 2014, 35(6), 806-813.
33. Yi, S.; Chen, Y.; Wen, L.; Yang, L.; Cui, G., Downregulation of nucleoporin 88 and 214 induced by oridonin may protect OCIM2 acute erythroleukemia cells from apoptosis through regulation of nucleocytoplasmic transport of NF-kappa B. Int. J. Molecul. Med., 2012, 30(4), 877-883.
34. Wang, Z.Y.; Chen, Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood, 2008, 111(5), 2505-2515.
35. Dos Santos, G.A.; Kats, L.; Pandolfi, P.P. Synergy against PMLRARa: targeting transcription, proteolysis, differentiation, and selfrenewal in acute promyelocytic leukemia. J. Experiment. Med., 2013, 210(13), 2793-2802.
36. Gao, F.; Tang, Q.; Yang, P.; Fang, Y.; Li, W.; Wu, Y. Apoptosis inducing and differentiation enhancement effect of oridonin on the all-trans-retinoic acid-sensitive and-resistant acute promyelocytic leukemia cells. Int. J. Lab. Hematol., 2010, 32(1), E114-E122.
37. Kastner, P.; Chan, S. Function of RAR alpha during the maturation of neutrophils. Oncogene, 2001, 20(49), 7178-7185.
38. Klejman, A.; Schreiner, S.J.; Nieborowska-Skorska, M.; Slupianek, A.; Wilson, M.; Smithgall, T.E.; Skorski, T. The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells. EMBO J., 2002, 21(21), 5766-5774.
39. Guo, Y.; Shan, Q.; Gong, Y.; Lin, J.; Yang, X.; Zhou, R. Oridonin in combination with imatinib exerts synergetic anti-leukemia effects in Ph+ acute lymphoblastic leukemia cells in vitro by inhibiting activation of LYN/mTOR signaling pathway. Cancer Biol. Therap., 2012, 13(13), 1244-1254.
40. Steelman, L.S.; Abrams, S.L.; Whelan, J.; Bertrand, F.E.; Ludwig, D.E.; Basecke, J.; Libra, M.; Stivala, F.; Milella, M.; Tafuri, A.; Lunghi, P.; Bonati, A.; Martelli, A.M.; McCubrey, J.A. Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia. Leukemia, 2008, 22(4), 686-707.
41. Hoelbl, A.; Schuster, C.; Kovacic, B.; Zhu, B.; Wickre, M.; Hoelzl, M.A.; Fajmann, S.; Grebien, F.; Warsch, W.; Stengl, G.; Hennighausen, L.; Poli, V.; Beug, H.; Moriggl, R.; Sexl, V. Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia. EMBO Molecul. Med., 2010, 2(3), 98-110.
42. Hu, Y.; Liu, Y.; Pelletier, S.; Buchdunger, E.; Warmuth, M.; Fabbro, D.; Hallek, M.; Van Etten, R.A.; Li, S. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced Blymphoblastic leukemia but not chronic myeloid leukemia. Nature Genet., 2004, 36(5), 453-461.
43. Guo, Y.; Shan, Q.; Gong, Y.; Lin, J.; Yang, X.; Zhou, R. Antileukemia effect of oridonin on Ph+ acute lymphoblastic leukemia cell SUP-B15. Chinese J. Hematol., 2012, 33(6), 439-443.
44. Pelicano, H.; Carney, D.; Huang, P. ROS stress in cancer cells and therapeutic implications. Drug Resist. Update, 2004, 7(2), 97-110.
45. Murphy, M.P., How mitochondria produce reactive oxygen species. Biochemical J., 2009, 417, 1-13.
46. Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.D.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
47. Droge, W., Free radicals in the physiological control of cell function. Physiologic. Rev., 2002, 82(1), 47-95.
48. Hileman, E.O.; Liu, J.S.; Albitar, M.; Keating, M.J.; Huang, P., Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity. Cancer Chemotherap. Pharmacol., 2004, 53(3), 209-219.
49. Zang, L.H.; He, H.; Xu, Q.; Yu, Y.; Zheng, N.; Liu, W.W.; Hayashi, T.; Tashiro, S.; Onodera, S.; Ikejima, T. Reactive oxygen species H2O2 and center dot OH, but not O-2 center dot(-) promote oridonin-induced phagocytosis of apoptotic cells by human histocytic lymphoma U937 cells. Int. Immunopharmacol., 2013, 15(2), 414-423.
50. Zeng, R.; Chen, Y.; Zhao, S.; Cui, G.-H. Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitro via regulating intracellular ROS and SIRT1. Acta Pharmacologica Sinica, 2012, 33(1), 91-100.
51. Haddad, J.J. Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors. Cell Signal., 2002, 14(11), 879-897.
52. Wang, L.; Zhao, W.L.; Yan, J.S.; Liu, P.; Sun, H.P.; Zhou, G.B.; Weng, Z.Y.; Wu, W.L.; Weng, X.Q.; Sun, X.J.; Chen, Z.; Sun, H.D.; Chen, S.J. Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappa B and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death Differentiation, 2007, 14(2), 306-317.
53. Liu, J.J.; Huang, R.W.; Lin, D.J.; Wu, X.Y.; Peng, J.; Lin, Q.; Pan, X.L.; Zhang, M.H.; Hou, M.; Chen, F. Apoptotic effect of oridonin on NB4 cells and its mechanism. Leukem. Lymphoma, 2005, 46(4), 593-597.
54. Liu, Y.Q.; You, S.; Tashiro, S.; Onodera, S.; Ikejima, T. Activation of phosphoinositide 3-kinase, protein kinase C, and extracellular signal-regulated kinase is required for oridonin-enhanced phagocytosis of apoptotic bodies in human macrophage-like U937 cells. J. Pharmacologic. Sci., 2005, 98(4), 361-371.
55. Kondo, Y.; Kanzawa, T.; Sawaya, R.; Kondo, S. The role of autophagy in cancer development and response to therapy. Nature Rev. Cancer, 2005, 5(9), 726-734.
56. Nikoletopoulou, V.; Markaki, M.; Palikaras, K.; Tavernarakis, N. Crosstalk between apoptosis, necrosis and autophagy. Biochim. Et Biophysic. Acta, 2013, 1833(12), 3448-3459.
57. Wagner, E.F.; Nebreda, A.R. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat. Rev. Cancer, 2009, 9(8), 537-549.
58. Roux, P.P.; Blenis, J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev., 2004, 68(2), 320-+.
59. Kyriakis, J.M.; Avruch, J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiologic. Rev., 2001, 81(2), 807-869.
60. Pearson, G.; Robinson, F.; Gibson, T.B.; Xu, B.E.; Karandikar, M.; Berman, K.; Cobb, M.H. Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr. Rev., 2001, 22(2), 153-183.
61. Milella, M.; Kornblau, S.M.; Estrov, Z.; Carter, B.Z.; Lapillonne, H.; Harris, D.; Konopleva, M.; Zhao, S.R.; Estey, E.; Andreeff, M. Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia. J. Clin. Investigat., 2001, 108(6), 851-859.
62. Kohno, M.; Pouyssegur, J. Pharmacological inhibitors of the ERK signaling pathway: application as anticancer drugs. Prog. Cell Cycle Res., 2003, 5, 219-224.
63. Liu, Y.-Q.; Mu, Z.-Q.; You, S.; Tashiro, S.-I.; Onodera, S.; Ikejima, T. Fas/FasL signaling allows extracelluar-signal regulated kinase to regulate cytochrome c release in oridonin-induced apoptotic U937 cells. Biologic. Pharmaceut. Bullet., 2006, 29(9), 1873-1879.
64. Liu, Y.-Q.; You, S.; Tashiro, S.-I.; Onodera, S.; Ikejima, T. Oridonin induced U937 cell apoptosis through ERK pathway. China J. Chinese Materia Medic., 2005, 30(23), 1856-1859.
65. Liu, Y.-Q.; You, S.; Tashiro, S.-I.; Onodera, S.; Ikejima, T. Regulation of ERK MAPK in oridonin-enhanced phagocytosis of apoptotic bodies in human macrophage-like U937 cells. Zhongguo Yaolixue Tongbao, 2006, 22(1), 110-113.
66. Liu, Y.Q.; You, S.; Tashiro, S.I.; Onodera, S.; Ikejima, T. Roles of Ras and extracellular signal-regulated kinase-dependent I kappa B alpha degradation in oridonin-enhanced phagocytosis of apoptotic cells by human macrophage-like U937 cells. Int. Immunopharmacol., 2006, 6(2), 260-268.
67. Zang, L.; Xu, Q.; Ye, Y.; Li, X.; Liu, Y.; Tashiro, S.-I.; Onodera, S.; Ikejima, T. Autophagy enhanced phagocytosis of apoptotic cells by oridonin-treated human histocytic lymphoma U937 cells. Archiv. Biochem. Biophysic., 2012, 518(1), 31-41.
68. Zang, L.; He, H.; Ye, Y.; Liu, W.; Fan, S.; Tashiro, S.-I.; Onodera, S.; Ikejima, T., Nitric oxide augments oridonin-induced eff erocytosis by human histocytic lymphoma U937 cells via autophagy and the NF-kappa B-COX-2-IL-1 beta pathway. Free Radical Res., 2012, 46(10), 1207-1219.
69. Cai, D.-T.; Jin, H.; Xiong, Q.-X.; Liu, W.-G.; Gao, Z.-G.; Gu, G.-X.; Qiu, Y.-H, ER stress and ASK1-JNK activation contribute to oridonin-induced apoptosis and growth inhibition in cultured human hepatoblastoma HuH-6 cells. Mol. Cell. Biochem., 2013, 379(1-2), 161-169.
70. Wang, H.; Ye, Y.; Chu, J.-H.; Zhu, G.-Y.; Li, Y.-W.; Fong, D.W.F.; Yu, Z.-L. Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells. Oncol. Reports, 2010, 24(3), 647-651.
71. Cheng, Y.; Qiu, F.; Ye, Y.-C.; Tashiro, S.-I.; Onodera, S.; Ikejima, T. Oridonin induces G(2)/M arrest and apoptosis via activating ERK-p53 apoptotic pathway and inhibiting PTK-Ras-Raf-JNK survival pathway in murine fibrosarcoma L929 cells. Archiv. Biochem. Biophysic., 2009, 490(1), 70-75.
72. Fresno Vara, J.A.; Casado, E.; de Castro, J.; Cejas, P.; Belda-Iniesta, C.; Gonzalez-Baron, M., PI3K/Akt signalling pathway and cancer. Cancer Treatment Rev., 2004, 30(2), 193-204.
73. Burris, H.A. 3rd, Overcoming acquired resistance to anticancer therapy: focus on the PI3K/AKT/mTOR pathway. Cancer Chemother Pharmacol, 2013, 71(4), 829-842.
74. Mendoza, M.C.; Er, E.E.; Blenis, J. The Ras-ERK and PI3KmTOR pathways: cross-talk and compensation. Trends Biochem. Sci., 2011, 36(6), 320-328.
75. Vasudevan, S.; Tong, Y.; Steitz, J.A. Switching from repression to activation: microRNAs can up-regulate translation. Science, 2007, 318(5858), 1931-1934.
76. Deng, S.; Calin, G.A.; Croce, C.M.; Coukos, G.; Zhang, L. Mechanisms of microRNA deregulation in human cancer. Cell Cycle, 2008, 7(17), 2643-2646.
77. Calin, G.A.; Croce, C.M. MicroRNA signatures in human cancers. Nat .Rev. Cancer, 2006, 6(11), 857-866.
78. Davis, C.D.; Ross, S.A. Evidence for dietary regulation of microRNA expression in cancer cells. Nutrition Rev., 2008, 66(8), 477-482.
79. Huang, H.L.; Weng, H.Y.; Wang, L.Q.; Yu, C.H.; Huang, Q.J.; Zhao, P.P.; Wen, J.Z.; Zhou, H.; Qu, L.H. Triggering Fbw7-mediated proteasomal degradation of c-Myc by oridonin induces cell growth inhibition and apoptosis. Mol. Cancer Ther., 2012, 11(5), 1155-1165.
80. Weng, H.; Huang, H.; Dong, B.; Zhao, P.; Zhou, H.; Qu, L. Inhibition of miR-17 and miR-20a by oridonin triggers apoptosis and reverses chemoresistance by derepressing BIM-S. Cancer Res., 2014, 74(16), 4409-4419.
81. Venturini, L.; Battmer, K.; Castoldi, M.; Schultheis, B.; Hochhaus, A.; Muckenthaler, M.U.; Ganser, A.; Eder, M.; Scherr, M. Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. Blood, 2007, 109(10), 4399-4405.