Tel.: 510-420-4167, Fax: 510-420-4197
Cancer Therapy
Selective concomitant inhibition of mTORC1 and mTORC2 activity in estrogen receptor negative breast cancer cells by BN107 and oleanolic acid†
Article first published online: 21 DEC 2009
DOI: 10.1002/ijc.25116
Copyright © 2009 UICC
Additional Information
How to Cite
Chu, R., Zhao, X., Griffin, C., Staub, R. E., Shoemaker, M., Climent, J., Leitman, D., Cohen, I., Shtivelman, E. and Fong, S. (2010), Selective concomitant inhibition of mTORC1 and mTORC2 activity in estrogen receptor negative breast cancer cells by BN107 and oleanolic acid. Int. J. Cancer, 127: 1209–1219. doi: 10.1002/ijc.25116
- †
Conflict of interest: Ruth Chu, Xiaoyue Zhao, Richard E. Staub, Mark Shoemaker, Isaac Cohen, Emma Shtivelman and Sylvia Fong are employees of Bionovo Inc. that supported the work carried out in this article.
Publication History
- Issue published online: 25 JUN 2010
- Article first published online: 21 DEC 2009
- Manuscript Accepted: 26 NOV 2009
- Manuscript Received: 13 MAY 2009
References
- 1, , , , , , , , , . Inhibition of proteasome activity in Gleditsia sinensis fruit extract-mediated apoptosis on human carcinoma cells. Int J Mol Med 2005; 16: 925–9.
- 2, , , , , , , , , , , , et al. Gleditsia sinensis fruit extract-induced apoptosis involves changes of reactive oxygen species level, mitochondrial membrane depolarization and caspase 3 activation. Int J Mol Med 2005; 15: 539–43.
- 3, , , . The inhibitory effect of Gleditsia sinensis on cyclooxygenase-2 expression in human esophageal squamous cell carcinoma. Int J Mol Med 2009; 23: 121–9.
- 4, , , , . In vitro anticancer activity of twelve Chinese medicinal herbs. Phytother Res 2005; 19: 649–51.Direct Link:
- 5, , , , . Structure-activity relationships of saponins from Gleditsia sinensis in cytotoxicity and induction of apoptosis. Planta. Med. 2004; 70: 797–802.
- 6, , . Effects of oleanolic acid and ursolic acid on inhibiting tumor growth and enhancing the recovery of hematopoietic system postirradiation in mice. Cancer Lett 1997; 111: 7–13.
- 7, , . Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat Rev Cancer 2007; 7: 357–69.
- 8, , . Investigations of the mechanism of membrane activity of selected triterpenoid saponins. Planta Med 2001; 67: 43–8.
- 9, . Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 2000; 1: 31–9.
- 10, . Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies. Biochim Biophys Acta 2007; 1768: 1311–24.
- 11. Dissecting lipid raft facilitated cell signaling pathways in cancer. Biochim Biophys Acta 2008; 1785: 182–206.
- 12Transendothelial movement and caveolae. Nat Biotechnol 2008; 26: 380–1; author reply 1–2.
- 13, , , , , , , . Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Res 2007; 67: 6238–46.
- 14, , , , , , . Targeting lipid rafts inhibits protein kinase B by disrupting calcium homeostasis and attenuates malignant properties of melanoma cells. Carcinogenesis 2008; 29: 1546–54.
- 15, , , , . Localization of translational components at the ultramicroscopic level at postsynaptic sites of the rat brain. Brain Res 2003; 972: 168–76.
- 16, , , , . Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells. Mol Cell 2008; 32: 140–9.
- 17, , , , , , , , . Dissection of signaling pathways in fourteen breast cancer cell lines using reverse-phase protein lysate microarray. Technol Cancer Res Treat 2006; 5: 543–51.
- 18, , , . The role of mTOR in the management of solid tumors: an overview. Cancer Treat Rev 2008.
- 19, , , , , , , , , , . Akt as a therapeutic target in cancer. Expert Opin Ther Targets 2008; 12: 1139–65.
- 20, , , . Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307: 1098–101.
- 21, , , , . Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation. Biochem J 1999; 344 Pt 2: 427–31.
- 22, . Stress and mTORture signaling. Oncogene 2006; 25: 6373–83.
- 23. mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 2006; 6: 729–34.
- 24, . A complex interplay between Akt. TSC2 and the two m. TOR complexes. Biochem Soc Trans 2009; 37: 217–22.
- 25, , , , , , , , , . Identification of Protor as a novel Rictor-binding component of mTOR complex-2. Biochem J 2007; 405: 513–22.
- 26, . mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J 2008; 416: 375–85.
- 27, , . New insights into mTOR signaling: mTORC2 and beyond. Sci Signal 2009; 2: pe27.
- 28, , . Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005; 17: 596–603.
- 29, . The two TORCs and Akt. Dev Cell 2007; 12: 487–502.
- 30, . Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9–22.
- 31, , . TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res 2009; 69: 1821–7.
- 32
- 33, , , . mTORC1 inhibitors: is temsirolimus in renal cancer telling us how they really work? Br J Cancer 2008; 99: 1197–203.
- 34, , , , , , , . Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22: 159–68.
- 35, , , . PI3K inhibitors for cancer treatment: where do we stand? Biochem Soc Trans 2009; 37: 265–72.
- 36, , , , , , , Timosaponin AIII is preferentially cytotoxic to tumor cells through inhibition of mTOR and induction of ER stress. PloS one 2009; 4: e7283.
- 37, , , , . Lipid rafts remodeling in estrogen receptor-negative breast cancer is reversed by histone deacetylase inhibitor. Mol Cancer Ther 2006; 5: 238–45.
- 38, , , , , , . Resistance to antiestrogen arzoxifene is mediated by overexpression of cyclin D1. Mol Endocrinol 2009; 23: 1335–45.
- 39, . Increased proteasome-dependent degradation of estrogen receptor-alpha by TGF-beta1 in breast cancer cell lines. J Cell Biochem 2003; 88: 181–90.Direct Link:
- 40, , . Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nat Rev Drug Discov 2007; 6: 541–55.
- 41, . Farnesol and geranylgeraniol: prevention and reversion of lovastatin-induced effects in NIH3T3 cells. Lipids 2002; 37: 185–92.
- 42, , , , , , . Alteration of Na+ permeability in human erythrocytes as studied by 23Na-NMR and inhibition of the kidney Na+,K+-ATPase activities with saponins: interaction of gleditsia saponins with human erythrocyte membranes. Bioorg Med Chem Lett 1995; 5: 827–30.
- 43, , , , , , , . Molecular mechanisms underlying selective cytotoxic activity of BZL101, an extract of Scutellaria barbata, towards breast cancer cells. Cancer Biol Ther 2008; 7: 577–86.
- 44, , , . CD44 engagement promotes matrix-derived survival through the CD44-SRC-integrin axis in lipid rafts. Mol Cell Biol 2008; 28: 5710–23.
- 45, , , , . Caveolin regulation of endothelial function. Am J Physiol Lung Cell Mol Physiol 2003; 285: L1179–83.
- 46, . Lipid rafts in health and disease. Biol Cell 2007; 99: 129–40.
- 47, , , , , , , , , , , , et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006; 10: 515–27.
- 48, , , , , , Short-term effects of pure anti-oestrogen ICI 182780 treatment on oestrogen receptor, epidermal growth factor receptor and transforming growth factor-alpha protein expression in human breast cancer. Eur J Cancer 1996; 32A: 413–6.
- 49. Lipid rafts: heterogeneity on the high seas. Biochem J 2004; 378: 281–92.
- 50, , , , , , . Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol 2009; 7: e38.
- 51, , , , , , , , , . An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem 2009; 284: 8023–32.
- 52, , , , . Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 2001; 294: 1942–5.
- 53, . Targeting mTOR with rapamycin: one dose does not fit all. Cell Cycle 2009; 8: 1026–9.
- 54, , , , , . Regulation of mTORC1 and mTORC2 complex assembly by phosphatidic acid: competition with rapamycin. Mol Cell Biol 2009; 29: 1411–20.
- 55, , . Cholesterol and cholesterol-rich membranes in prostate cancer: an update. Tumori 2008; 94: 633–9.
- 56
- 57, , . Membrane rafts as potential sites of nongenomic hormonal signaling in prostate cancer. Trends Endocrinol Metab 2005; 16: 273–9.
- 58, . Role of cholesterol and lipid organization in disease. Nature 2005; 438: 612–21.
- 59, . Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins. Eur J Pharm Biopharm 2005; 61: 115–25.
- 60, , . Lipid rafts: at a crossroad between cell biology and physics. Nat Cell Biol 2007; 9: 7–14.
- 61, , , , , , . Asymmetric localization of flotillins/reggies in preassembled platforms confers inherent polarity to hematopoietic cells. Proc Natl Acad Sci USA 2003; 100: 8241–6.

1097-0215/asset/olbannerleft.jpg?v=1&s=45719cd7de57873027993264fcc568b335a8cd56)
1097-0215/asset/olbannerright.jpg?v=1&s=5e0fba63c1309b3036eb9215a0e1e83dd02efd19)
