Molecular mechanisms involved in farnesol-induced apoptosis

Cancer Letters

Volumn 287, Issue 2, 2010, Pages 123-135

  Joo, Joung Hyuck ^a   Jetten, Anton M ^a  

^a Division of Intramural Research   (United States)

Author keywords

Apoptosis; Apoptosome; Cancer; Chemoprevention; CTP:phosphocholine cytidylyltransferase; Endoplasmic reticulum stress; Farnesol; Isoprenoid; MAP kinase; NF B; Nuclear receptor; Unfolded protein response

Indexed keywords

APOPTOSOME; CELL NUCLEUS RECEPTOR; CITICOLINE; FARNESOID X RECEPTOR; FARNESOL; GERANIOL; GERANYLGERANIOL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; NEROLIDOL; PERILLYL ALCOHOL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; REACTIVE OXYGEN METABOLITE; THYROID HORMONE RECEPTOR BETA;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER INHIBITION; CELL CYCLE ARREST; CELL DIFFERENTIATION; CELL PROLIFERATION; CHEMOPROPHYLAXIS; CLINICAL TRIAL; COLON CARCINOGENESIS; DIET THERAPY; DRUG GLUCURONIDATION; DRUG SPECIFICITY; DRUG STRUCTURE; DRUG TARGETING; ENDOPLASMIC RETICULUM STRESS; GROWTH INHIBITION; HUMAN; KIDNEY TUMOR; NONHUMAN; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; SHORT SURVEY; SIGNAL TRANSDUCTION; SOLID TUMOR;

ANIMALIA;

EID: 73249114946     PISSN: 03043835     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.canlet.2009.05.015     Document Type: Review

References (160)

1. Hanley K., Komuves L.G., Ng D.C., Schoonjans K., He S.S., Lau P., Bikle D.D., Williams M.L., Elias P.M., Auwerx J., and Feingold K.R. Farnesol stimulates differentiation in epidermal keratinocytes via PPARalpha. J. Biol. Chem. 275 (2000) 11484-11491
2. Rioja A., Pizzey A.R., Marson C.M., and Thomas N.S. Preferential induction of apoptosis of leukaemic cells by farnesol. FEBS Lett. 467 (2000) 291-295
3. Bifulco M. Role of the isoprenoid pathway in ras transforming activity, cytoskeleton organization, cell proliferation and apoptosis. Life Sci. 77 (2005) 1740-1749
4. Miquel K., Pradines A., and Favre G. Farnesol and geranylgeraniol induce actin cytoskeleton disorganization and apoptosis in A549 lung adenocarcinoma cells. Biochem. Biophys. Res. Commun. 225 (1996) 869-876
5. Wright M.M., Henneberry A.L., Lagace T.A., Ridgway N.D., and McMaster C.R. Uncoupling farnesol-induced apoptosis from its inhibition of phosphatidylcholine synthesis. J. Biol. Chem. 276 (2001) 25254-25261
6. McTaggart S.J. Isoprenylated proteins. Cell. Mol. Life Sci. 63 (2006) 255-267
7. Ong T.P., Heidor R., de Conti A., Dagli M.L., and Moreno F.S. Farnesol and geraniol chemopreventive activities during the initial phases of hepatocarcinogenesis involve similar actions on cell proliferation and DNA damage, but distinct actions on apoptosis, plasma cholesterol and HMGCoA reductase. Carcinogenesis 27 (2006) 1194-1203
8. Goldstein J.L., and Brown M.S. Regulation of the mevalonate pathway. Nature 343 (1990) 425-430
9. Edwards P.A., and Ericsson J. Sterols and isoprenoids: signaling molecules derived from the cholesterol biosynthetic pathway. Annu. Rev. Biochem. 68 (1999) 157-185
10. Roskoski Jr. R. Protein prenylation: a pivotal posttranslational process. Biochem. Biophys. Res. Commun. 303 (2003) 1-7
11. Burke Y.D., Stark M.J., Roach S.L., Sen S.E., and Crowell P.L. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids 32 (1997) 151-156
12. Crowell P.L. Prevention and therapy of cancer by dietary monoterpenes. J. Nutr. 129 (1999) 775S-778S
13. McGarvey D.J., and Croteau R. Terpenoid metabolism. Plant Cell 7 (1995) 1015-1026
14. Adany I., Yazlovitskaya E.M., Haug J.S., Voziyan P.A., and Melnykovych G. Differences in sensitivity to farnesol toxicity between neoplastically- and non-neoplastically-derived cells in culture. Cancer Lett. 79 (1994) 175-179
15. Yazlovitskaya E.M., and Melnykovych G. Selective farnesol toxicity and translocation of protein kinase C in neoplastic HeLa-S3K and non-neoplastic CF-3 cells. Cancer Lett. 88 (1995) 179-183
16. Melnykovych G., Haug J.S., and Goldner C.M. Growth inhibition of leukemia cell line CEM-C1 by farnesol: effects of phosphatidylcholine and diacylglycerol. Biochem. Biophys. Res. Commun. 186 (1992) 543-548
17. J.H. Joo, C. Bortner, A.M. Jetten, Induction of apoptosis in T-lymphoblastic leukemia MOLT4 cells by farnesol, Unpublished observations.
18. Wiseman D.A., Werner S.R., and Crowell P.L. Cell cycle arrest by the isoprenoids perillyl alcohol, geraniol, and farnesol is mediated by p21(Cip1) and p27(Kip1) in human pancreatic adenocarcinoma cells. J. Pharmacol. Exp. Ther. 320 (2007) 1163-1170
19. Joo J.H., Liao G., Collins J.B., Grissom S.F., and Jetten A.M. Farnesol-induced apoptosis in human lung carcinoma cells is coupled to the endoplasmic reticulum stress response. Cancer Res. 67 (2007) 7929-7936
20. Miquel K., Pradines A., Terce F., Selmi S., and Favre G. Competitive inhibition of choline phosphotransferase by geranylgeraniol and farnesol inhibits phosphatidylcholine synthesis and induces apoptosis in human lung adenocarcinoma A549 cells. J. Biol. Chem. 273 (1998) 26179-26186
21. He L., Mo H., Hadisusilo S., Qureshi A.A., and Elson C.E. Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J. Nutr. 127 (1997) 668-674
22. Xu M., Floyd H.S., Greth S.M., Chang W.C., Lohman K., Stoyanova R., Kucera G.L., Kute T.E., Willingham M.C., and Miller M.S. Perillyl alcohol-mediated inhibition of lung cancer cell line proliferation: potential mechanisms for its chemotherapeutic effects. Toxicol. Appl. Pharmacol. 195 (2004) 232-246
23. Yu S.G., Hildebrandt L.A., and Elson C.E. Geraniol, an inhibitor of mevalonate biosynthesis, suppresses the growth of hepatomas and melanomas transplanted to rats and mice. J. Nutr. 125 (1995) 2763-2767
24. Sahin M.B., Perman S.M., Jenkins G., and Clark S.S. Perillyl alcohol selectively induces G0/G1 arrest and apoptosis in Bcr/Abl-transformed myeloid cell lines. Leukemia 13 (1999) 1581-1591
25. Elegbede J.A., Flores R., and Wang R.C. Perillyl alcohol and perillaldehyde induced cell cycle arrest and cell death in BroTo and A549 cells cultured in vitro. Life Sci. 73 (2003) 2831-2840
26. Shi W., and Gould M.N. Induction of cytostasis in mammary carcinoma cells treated with the anticancer agent perillyl alcohol. Carcinogenesis 23 (2002) 131-142
27. Rajesh D., and Howard S.P. Perillyl alcohol mediated radiosensitization via augmentation of the Fas pathway in prostate cancer cells. Prostate 57 (2003) 14-23
28. Au-Yeung K.K., Liu P.L., Chan C., Wu W.Y., Lee S.S., and Ko J.K. Herbal isoprenols induce apoptosis in human colon cancer cells through transcriptional activation of PPARgamma. Cancer Invest. 26 (2008) 708-717
29. Duncan R.E., Lau D., El-Sohemy A., and Archer M.C. Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity. Biochem. Pharmacol. 68 (2004) 1739-1747
30. Scheper M.A., Shirtliff M.E., Meiller T.F., Peters B.M., and Jabra-Rizk M.A. Farnesol a fungal quorum-sensing molecule triggers apoptosis in human oral squamous carcinoma cells. Neoplasia 10 (2008) 954-963
31. Malumbres M., and Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev. Cancer 9 (2009) 153-166
32. Yeruva L., Pierre K.J., Elegbede A., Wang R.C., and Carper S.W. Perillyl alcohol and perillic acid induced cell cycle arrest and apoptosis in non-small cell lung cancer cells. Cancer Lett. 257 (2007) 216-226
33. Greider C., Chattopadhyay A., Parkhurst C., and Yang E. BCL-x(L) and BCL2 delay Myc-induced cell cycle entry through elevation of p27 and inhibition of G1 cyclin-dependent kinases. Oncogene 21 (2002) 7765-7775
34. Janumyan Y., Cui Q., Yan L., Sansam C.G., Valentin M., and Yang E. G0 function of BCL2 and BCL-xL requires BAX, BAK, and p27 phosphorylation by Mirk, revealing a novel role of BAX and BAK in quiescence regulation. J. Biol. Chem. 283 (2008) 34108-34120
35. Taylor M.M., Macdonald K., Morris A.J., and McMaster C.R. Enhanced apoptosis through farnesol inhibition of phospholipase D signal transduction. Febs J. 272 (2005) 5056-5063
36. Ariazi E.A., Satomi Y., Ellis M.J., Haag J.D., Shi W., Sattler C.A., and Gould M.N. Activation of the transforming growth factor beta signaling pathway and induction of cytostasis and apoptosis in mammary carcinomas treated with the anticancer agent perillyl alcohol. Cancer Res. 59 (1999) 1917-1928
37. Lagace T.A., Miller J.R., and Ridgway N.D. Caspase processing and nuclear export of CTP:phosphocholine cytidylyltransferase alpha during farnesol-induced apoptosis. Mol. Cell. Biol. 22 (2002) 4851-4862
38. Lagace T.A., and Ridgway N.D. Induction of apoptosis by lipophilic activators of CTP:phosphocholine cytidylyltransferase alpha (CCTalpha). Biochem. J. 392 (2005) 449-456
39. Burke Y.D., Ayoubi A.S., Werner S.R., McFarland B.C., Heilman D.K., Ruggeri B.A., and Crowell P.L. Effects of the isoprenoids perillyl alcohol and farnesol on apoptosis biomarkers in pancreatic cancer chemoprevention. Anticancer Res. 22 (2002) 3127-3134
40. Clark S.S., Perman S.M., Sahin M.B., Jenkins G.J., and Elegbede J.A. Antileukemia activity of perillyl alcohol (POH): uncoupling apoptosis from G0/G1 arrest suggests that the primary effect of POH on Bcr/Abl-transformed cells is to induce growth arrest. Leukemia 16 (2002) 213-222
41. Unlu S., Mason C.D., Schachter M., and Hughes A.D. Perillyl alcohol, an inhibitor of geranylgeranyl transferase, induces apoptosis of immortalized human vascular smooth muscle cells in vitro. J. Cardiovasc. Pharmacol. 35 (2000) 341-344
42. Ohizumi H., Masuda Y., Nakajo S., Sakai I., Ohsawa S., and Nakaya K. Geranylgeraniol is a potent inducer of apoptosis in tumor cells. J. Biochem. (Tokyo) 117 (1995) 11-13
43. Stark Jr. W.W., Blaskovich M.A., Johnson B.A., Qian Y., Vasudevan A., Pitt B., Hamilton A.D., Sebti S.M., and Davies P. Inhibiting geranylgeranylation blocks growth and promotes apoptosis in pulmonary vascular smooth muscle cells. Am. J. Physiol. 275 (1998) L55-63
44. Carnesecchi S., Schneider Y., Ceraline J., Duranton B., Gosse F., Seiler N., and Raul F. Geraniol, a component of plant essential oils, inhibits growth and polyamine biosynthesis in human colon cancer cells. J. Pharmacol. Exp. Ther. 298 (2001) 197-200
45. Haag J.D., and Gould M.N. Mammary carcinoma regression induced by perillyl alcohol, a hydroxylated analog of limonene. Cancer Chemother. Pharmacol. 34 (1994) 477-483
46. Mills J.J., Chari R.S., Boyer I.J., Gould M.N., and Jirtle R.L. Induction of apoptosis in liver tumors by the monoterpene perillyl alcohol. Cancer Res. 55 (1995) 979-983
47. Stayrook K.R., McKinzie J.H., Burke Y.D., Burke Y.A., and Crowell P.L. Induction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells. Carcinogenesis 18 (1997) 1655-1658
48. Belanger J.T. Perillyl alcohol: applications in oncology. Altern. Med. Rev. 3 (1998) 448-457
49. Staines A.G., Sindelar P., Coughtrie M.W., and Burchell B. Farnesol is glucuronidated in human liver, kidney and intestine in vitro, and is a novel substrate for UGT2B7 and UGT1A1. Biochem. J. 384 (2004) 637-645
50. Horn T.L., Long L., Cwik M.J., Morrissey R.L., Kapetanovic I.M., and McCormick D.L. Modulation of hepatic and renal drug metabolizing enzyme activities in rats by subchronic administration of farnesol. Chem. Biol. Interact. 152 (2005) 79-99
51. Jahangir T., Khan T.H., Prasad L., and Sultana S. Farnesol prevents Fe-NTA-mediated renal oxidative stress and early tumour promotion markers in rats. Hum. Exp. Toxicol. 25 (2006) 235-242
52. Rao C.V., Newmark H.L., and Reddy B.S. Chemopreventive effect of farnesol and lanosterol on colon carcinogenesis. Cancer Detect. Prev. 26 (2002) 419-425
53. Wargovich M.J., Jimenez A., McKee K., Steele V.E., Velasco M., Woods J., Price R., Gray K., and Kelloff G.J. Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis 21 (2000) 1149-1155
54. Jahangir T., and Sultana S. Benzo(a)pyrene-induced genotoxicity: attenuation by farnesol in a mouse model. J. Enzyme Inhib. Med. Chem. 23 (2008) 888-894
55. Ripple G.H., Gould M.N., Stewart J.A., Tutsch K.D., Arzoomanian R.Z., Alberti D., Feierabend C., Pomplun M., Wilding G., and Bailey H.H. Phase I clinical trial of perillyl alcohol administered daily. Clin. Cancer Res. 4 (1998) 1159-1164
56. Ripple G.H., Gould M.N., Arzoomanian R.Z., Alberti D., Feierabend C., Simon K., Binger K., Tutsch K.D., Pomplun M., Wahamaki A., Marnocha R., Wilding G., and Bailey H.H. Phase I clinical and pharmacokinetic study of perillyl alcohol administered four times a day. Clin. Cancer Res. 6 (2000) 390-396
57. Bailey H.H., Wilding G., Tutsch K.D., Arzoomanian R.Z., Alberti D., Feierabend C., Simon K., Marnocha R., Holstein S.A., Stewart J., Lewis K.A., and Hohl R.J. A phase I trial of perillyl alcohol administered four times daily for 14 days out of 28 days. Cancer Chemother. Pharmacol. 54 (2004) 368-376
58. Hudes G.R., Szarka C.E., Adams A., Ranganathan S., McCauley R.A., Weiner L.M., Langer C.J., Litwin S., Yeslow G., Halberr T., Qian M., and Gallo J.M. Phase I pharmacokinetic trial of perillyl alcohol (NSC 641066) in patients with refractory solid malignancies. Clin. Cancer Res. 6 (2000) 3071-3080
59. Morgan-Meadows S., Dubey S., Gould M., Tutsch K., Marnocha R., Arzoomanin R., Alberti D., Binger K., Feierabend C., Volkman J., Ellingen S., Black S., Pomplun M., Wilding G., and Bailey H. Phase I trial of perillyl alcohol administered four times daily continuously. Cancer Chemother. Pharmacol. 52 (2003) 361-366
60. Azzoli C.G., Miller V.A., Ng K.K., Krug L.M., Spriggs D.R., Tong W.P., Riedel E.R., and Kris M.G. A phase I trial of perillyl alcohol in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 51 (2003) 493-498
61. Liu G., Oettel K., Bailey H., Ummersen L.V., Tutsch K., Staab M.J., Horvath D., Alberti D., Arzoomanian R., Rezazadeh H., McGovern J., Robinson E., DeMets D., and Wilding G. Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer. Invest. New Drugs 21 (2003) 367-372
62. Bailey H.H., Levy D., Harris L.S., Schink J.C., Foss F., Beatty P., and Wadler S. A phase II trial of daily perillyl alcohol in patients with advanced ovarian cancer: eastern cooperative oncology group study E2E96. Gynecol. Oncol. 85 (2002) 464-468
63. Bailey H.H., Attia S., Love R.R., Fass T., Chappell R., Tutsch K., Harris L., Jumonville A., Hansen R., Shapiro G.R., and Stewart J.A. Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer. Cancer Chemother. Pharmacol. 62 (2008) 149-157
64. Stearns V., Coop A., Singh B., Gallagher A., Yamauchi H., Lieberman R., Pennanen M., Trock B., Hayes D.F., and Ellis M.J. A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia. Clin. Cancer Res. 10 (2004) 7583-7591
65. Meadows S.M., Mulkerin D., Berlin J., Bailey H., Kolesar J., Warren D., and Thomas J.P. Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer. Int. J. Gastrointest. Cancer 32 (2002) 125-128
66. Schroepfer Jr. G.J. Sterol biosynthesis. Annu. Rev. Biochem. 50 (1981) 585-621
67. Nakanishi M., Goldstein J.L., and Brown M.S. Multivalent control of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mevalonate-derived product inhibits translation of mRNA and accelerates degradation of enzyme. J. Biol. Chem. 263 (1988) 8929-8937
68. Correll C.C., Ng L., and Edwards P.A. Identification of farnesol as the non-sterol derivative of mevalonic acid required for the accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. J. Biol. Chem. 269 (1994) 17390-17393
69. Meigs T.E., Roseman D.S., and Simoni R.D. Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase degradation by the nonsterol mevalonate metabolite farnesol in vivo. J. Biol. Chem. 271 (1996) 7916-7922
70. Meigs T.E., and Simoni R.D. Farnesol as a regulator of HMG-CoA reductase degradation: characterization and role of farnesyl pyrophosphatase. Arch. Biochem. Biophys. 345 (1997) 1-9
71. Brown A.J. Cholesterol, statins and cancer. Clin. Exp. Pharmacol. Physiol. 34 (2007) 135-141
72. Sassano A., and Platanias L.C. Statins in tumor suppression. Cancer Lett. 260 (2008) 11-19
73. Fritz G. HMG-CoA reductase inhibitors (statins) as anticancer drugs (review). Int. J. Oncol. 27 (2005) 1401-1409
74. Houten S.M., Frenkel J., and Waterham H.R. Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation. Cell. Mol. Life Sci. 60 (2003) 1118-1134
75. Mo H., and Elson C.E. Studies of the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy and chemoprevention. Exp. Biol. Med. (Maywood) 22 (2004) 567-585
76. Elson 76] C.E., Peffley D.M., Hentosh P., and Mo H. Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer. Proc. Soc. Exp. Biol. Med. 221 (1999) 294-311
77. Sebti S.M., and Hamilton A.D. Farnesyltransferase and geranylgeranyltransferase I inhibitors and cancer therapy: lessons from mechanism and bench-to-bedside translational studies. Oncogene 19 (2000) 6584-6593
78. Chen J.C., Wu M.L., Huang K.C., and Lin W.W. HMG-CoA reductase inhibitors activate the unfolded protein response and induce cytoprotective GRP78 expression. Cardiovasc. Res. 80 (2008) 138-150
79. Anthony M.L., Zhao M., and Brindle K.M. Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells. J. Biol. Chem. 274 (1999) 19686-19692
80. Voziyan P.A., Goldner C.M., and Melnykovych G. Farnesol inhibits phosphatidylcholine biosynthesis in cultured cells by decreasing cholinephosphotransferase activity. Biochem. J. 295 (1993) 757-762
81. Sciorra V.A., and Morris A.J. Roles for lipid phosphate phosphatases in regulation of cellular signaling. Biochim. Biophys. Acta 1582 (2002) 45-51
82. Vance J.E., and Vance D.E. Phospholipid biosynthesis in mammalian cells. Biochem. Cell Biol. 82 (2004) 113-128
83. Foster D.A., and Xu L. Phospholipase D in cell proliferation and cancer. Mol. Cancer Res. 1 (2003) 789-800
84. Newton A.C. Diacylglycerol's affair with protein kinase C turns 25. Trends Pharmacol. Sci. 25 (2004) 175-177
85. Cui Z., and Houweling M. Phosphatidylcholine and cell death. Biochim. Biophys. Acta 1585 (2002) 87-96
86. Jackowski S., and Fagone P. CTP: phosphocholine cytidylyltransferase: paving the way from gene to membrane. J. Biol. Chem. 280 (2005) 853-856
87. Cui Z., Houweling M., Chen M.H., Record M., Chap H., Vance D.E., and Terce F. A genetic defect in phosphatidylcholine biosynthesis triggers apoptosis in Chinese hamster ovary cells. J. Biol. Chem. 271 (1996) 14668-14671
88. Clement J.M., and Kent C. CTP:phosphocholine cytidylyltransferase: insights into regulatory mechanisms and novel functions. Biochem. Biophys. Res. Commun. 257 (1999) 643-650
89. Wang L., Magdaleno S., Tabas I., and Jackowski S. Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a). Mol. Cell. Biol. 25 (2005) 3357-3363
90. Li Z., and Vance D.E. Phosphatidylcholine and choline homeostasis. J. Lipid Res. 49 (2008) 1187-1194
91. Wang Y., Sweitzer T.D., Weinhold P.A., and Kent C. Nuclear localization of soluble CTP:phosphocholine cytidylyltransferase. J. Biol. Chem. 268 (1993) 5899-5904
92. Gehrig K., Cornell R.B., and Ridgway N.D. Expansion of the nucleoplasmic reticulum requires the coordinated activity of lamins and CTP:phosphocholine cytidylyltransferase alpha. Mol. Biol. Cell 19 (2008) 237-247
93. K. Gehrig, C.C. Morton, N.D. Ridgway, Nuclear export of the rate-limiting enzyme in phosphatidylcholine synthesis is mediated by its membrane binding domain, J. Lipid Res., in press.
94. Cornell R.B., and Northwood I.C. Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization. Trends Biochem. Sci. 25 (2000) 441-447
95. Henneberry A.L., Wright M.M., and McMaster C.R. The major sites of cellular phospholipid synthesis and molecular determinants of fatty acid and lipid head group specificity. Mol. Biol. Cell 13 (2002) 3148-3161
96. Wang Y., and Kent C. Effects of altered phosphorylation sites on the properties of CTP:phosphocholine cytidylyltransferase. J. Biol. Chem. 270 (1995) 17843-17849
97. Lagace T.A., and Ridgway N.D. The rate-limiting enzyme in phosphatidylcholine synthesis regulates proliferation of the nucleoplasmic reticulum. Mol. Cell. Biol. 16 (2005) 1120-1130
98. Wu J., and Kaufman R.J. From acute ER stress to physiological roles of the unfolded protein response. Cell Death Differ. 13 (2006) 374-384
99. Szegezdi E., Logue S.E., Gorman A.M., and Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 7 (2006) 880-885
100. Schroder M. Endoplasmic reticulum stress responses. Cell. Mol. Life Sci. 65 (2008) 862-894
101. Marciniak S.J., and Ron D. Endoplasmic reticulum stress signaling in disease. Physiol. Rev. 86 (2006) 1133-1149
102. Kim I., Xu W., and Reed J.C. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 7 (2008) 1013-1030
103. Vembar S.S., and Brodsky J.L. One step at a time: endoplasmic reticulum-associated degradation. Nat. Rev. Mol. Cell Biol. (2008) 944-957
104. Ron D., and Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8 (2007) 519-529
105. Yoshida H., Matsui T., Yamamoto A., Okada T., and Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107 (2001) 881-891
106. Joo J.H., and Jetten A.M. NF-kappaB-dependent transcriptional activation in lung carcinoma cells by farnesol involves p65/RelA(Ser276) phosphorylation via the MEK-MSK1 signaling pathway. J. Biol. Chem. 283 (2008) 16391-16399
107. Mungrue I.N., Pagnon J., Kohannim O., Gargalovic P.S., and Lusis A.J. CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. J. Immunol. 182 (2009) 466-476
108. Arai K., Lee S.R., van Leyen K., Kurose H., and Lo E.H. Involvement of ERK MAP kinase in endoplasmic reticulum stress in SH-SY5Y human neuroblastoma cells. J. Neurochem. 89 (2004) 232-239
109. Zhuang S., and Schnellmann R.G. A death-promoting role for extracellular signal-regulated kinase. J. Pharmacol. Exp. Ther. 319 (2006) 991-997
110. Riedl S.J., and Salvesen G.S. The apoptosome: signalling platform of cell death. Nat. Rev. Mol. Cell Biol. 8 (2007) 405-413
111. Ow Y.P., Green D.R., Hao Z., and Mak T.W. Cytochrome c: functions beyond respiration. Nat. Rev. Mol. Cell Biol. 9 (2008) 532-542
112. Li F., and Brattain M.G. Role of the survivin gene in pathophysiology. Am. J. Pathol. 169 (2006) 1-11
113. Matsukawa J., Matsuzawa A., Takeda K., and Ichijo H. The ASK1-MAP kinase cascades in mammalian stress response. J. Biochem. 136 (2004) 261-265
114. Urano F., Wang X., Bertolotti A., Zhang Y., Chung P., Harding H.P., and Ron D. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287 (2000) 664-666
115. Karin M., and Greten F.R. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5 (2005) 749-759
116. Todd D.J., Lee A.H., and Glimcher L.H. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat. Rev. Immunol. 8 (2008) 663-674
117. Zhang K., and Kaufman R.J. From endoplasmic-reticulum stress to the inflammatory response. Nature 454 (2008) 455-462
118. Kim R., Emi M., Tanabe K., and Murakami S. Role of the unfolded protein response in cell death. Apoptosis 11 (2006) 5-13
119. Yoshida H. ER stress and diseases. Febs J. 274 (2007) 630-658
120. Zhao L., and Ackerman S.L. Endoplasmic reticulum stress in health and disease. Curr. Opin. Cell Biol. 18 (2006) 444-452
121. Hu P., Han Z., Couvillon A.D., Kaufman R.J., and Exton J.H. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol. Cell. Biol. 26 (2006) 3071-3084
122. Deng J., Lu P.D., Zhang Y., Scheuner D., Kaufman R.J., Sonenberg N., Harding H.P., and Ron D. Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Mol. Cell. Biol. 24 (2004) 10161-10168
123. Wek R.C., Jiang H.Y., and Anthony T.G. Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 34 (2006) 7-11
124. Chen L.F., and Greene W.C. Shaping the nuclear action of NF-kappaB. Nat. Rev. Mol. Cell Biol. 5 (2004) 392-401
125. Vermeulen L., De Wilde G., Van Damme P., Vanden Berghe W., and Haegeman G. Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1). EMBO J. 22 (2003) 1313-1324
126. Fairn G.D., Macdonald K., and McMaster C.R. A chemogenomic screen in Saccharomyces cerevisiae uncovers a primary role for the mitochondria in farnesol toxicity and its regulation by the Pkc1 pathway. J. Biol. Chem. 282 (2007) 4868-4874
127. Machida K., and Tanaka T. Farnesol-induced generation of reactive oxygen species dependent on mitochondrial transmembrane potential hyperpolarization mediated by F(0)F(1)-ATPase in yeast. FEBS Lett. 462 (1999) 108-112
128. Machida K., Tanaka T., Fujita K., and Taniguchi M. Farnesol-induced generation of reactive oxygen species via indirect inhibition of the mitochondrial electron transport chain in the yeast Saccharomyces cerevisiae. J. Bacteriol. 180 (1998) 4460-4465
129. Machida K., Tanaka T., Yano Y., Otani S., and Taniguchi M. Farnesol-induced growth inhibition in Saccharomyces cerevisiae by a cell cycle mechanism. Microbiology 145 (1999) 293-299
130. Savoldi M., Malavazi I., Soriani F.M., Capellaro J.L., Kitamoto K., da Silva Ferreira M.E., Goldman M.H., and Goldman G.H. Farnesol induces the transcriptional accumulation of the Aspergillus nidulans Apoptosis-Inducing Factor (AIF)-like mitochondrial oxidoreductase. Mol. Microbiol. 70 (2008) 44-59
131. f.M.E. Shirtlif, B.P. Krom, R.A. Meijering, B.M. Peters, J. Zhu, M.A. Scheper, M.L. Harris, M.A. Jabra-Rizk, Farnesol-induced apoptosis in Candida albicans, Antimicrob. Agents Chemother., in press.
132. Qamar W., and Sultana S. Farnesol ameliorates massive inflammation, oxidative stress and lung injury induced by intratracheal instillation of cigarette smoke extract in rats: an initial step in lung chemoprevention. Chem. Biol. Interact. 176 (2008) 79-87
133. Forman B.M., Goode E., Chen J., Oro A.E., Bradley D.J., Perlmann T., Noonan D.J., Burka L.T., McMorris T., Lamph W.W., Evans R.M., and Weinberger C. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 81 (1995) 687-693
134. Seol W., Choi H.S., and Moore D.D. Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors. Mol. Endocrinol. 9 (1995) 72-85
135. Laffitte B.A., Kast H.R., Nguyen C.M., Zavacki A.M., Moore D.D., and Edwards P.A. Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J. Biol. Chem. 275 (2000) 10638-10647
136. Wang Y.D., Chen W.D., Moore D.D., and Huang W. FXR: a metabolic regulator and cell protector. Cell Res. 18 (2008) 1087-1095
137. Makishima M., Okamoto A.Y., Repa J.J., Tu H., Learned R.M., Luk A., Hull M.V., Lustig K.D., Mangelsdorf D.J., and Shan B. Identification of a nuclear receptor for bile acids. Science 284 (1999) 1362-1365
138. Parks D.J., Blanchard S.G., Bledsoe R.K., Chandra G., Consler T.G., Kliewer S.A., Stimmel J.B., Willson T.M., Zavacki A.M., Moore D.D., and Lehmann J.M. Bile acids: natural ligands for an orphan nuclear receptor. Science 284 (1999) 1365-1368
139. Wang H., Chen J., Hollister K., Sowers L.C., and Forman B.M. Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol. Cell 3 (1999) 543-553
140. Modica S., Murzilli S., Salvatore L., Schmidt D.R., and Moschetta A. Nuclear bile acid receptor FXR protects against intestinal tumorigenesis. Cancer Res. 68 (2008) 9589-9594
141. R.R. Maran, A. Thomas, M. Roth, Z. Shen, N. Esterly, D. Pinson, X. Gao, Y. Zhang, V. Ganapathy, F. Gonzalez, G.L. Guo, FXR deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development, J. Pharmacol. Exp. Ther., in press.
142. Kim I., Morimura K., Shah Y., Yang Q., Ward J.M., and Gonzalez F.J. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis 28 (2007) 940-946
143. De Gottardi A., Dumonceau J.M., Bruttin F., Vonlaufen A., Morard I., Spahr L., Rubbia-Brandt L., Frossard J.L., Dinjens W.N., Rabinovitch P.S., and Hadengue A. Expression of the bile acid receptor FXR in Barrett's esophagus and enhancement of apoptosis by guggulsterone in vitro. Mol. Cancer 5 (2006) 48
144. F. Journe, V. Durbecq, C. Chaboteaux, G. Rouas, G. Laurent, D. Nonclercq, C. Sotiriou, J.J. Body, D. Larsimont, Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients, Breast Cancer Res. Treat., in press.
145. Swales K.E., Korbonits M., Carpenter R., Walsh D.T., Warner T.D., and Bishop-Bailey D. The farnesoid X receptor is expressed in breast cancer and regulates apoptosis and aromatase expression. Cancer Res. 66 (2006) 10120-10126
146. Journe F., Laurent G., Chaboteaux C., Nonclercq D., Durbecq V., Larsimont D., and Body J.J. Farnesol, a mevalonate pathway intermediate, stimulates MCF-7 breast cancer cell growth through farnesoid-X-receptor-mediated estrogen receptor activation. Breast Cancer Res. Treat. 107 (2008) 49-61
147. Desvergne B., Michalik L., and Wahli W. Transcriptional regulation of metabolism. Physiol. Rev. 86 (2006) 465-514
148. Han S., and Roman J. Peroxisome proliferator-activated receptor gamma: a novel target for cancer therapeutics?. Anticancer Drugs 18 (2007) 237-244
149. Kostadinova R., Wahli W., and Michalik L. PPARs in diseases: control mechanisms of inflammation. Curr. Med. Chem. 12 (2005) 2995-3009
150. O'Brien M.L., Rangwala S.M., Henry K.W., Weinberger C., Crick D.C., Waechter C.J., Feller D.R., and Noonan D.J. Convergence of three steroid receptor pathways in the mediation of nongenotoxic hepatocarcinogenesis. Carcinogenesis 17 (1996) 185-190
151. Inoue I., Itoh F., Aoyagi S., Tazawa S., Kusama H., Akahane M., Mastunaga T., Hayashi K., Awata T., Komoda T., and Katayama S. Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem. Biophys. Res. Commun. 290 (2002) 131-139
152. Liliom K., Tsukahara T., Tsukahara R., Zelman-Femiak M., Swiezewska E., and Tigyi G. Farnesyl phosphates are endogenous ligands of lysophosphatidic acid receptors: inhibition of LPA GPCR and activation of PPARs. Biochim. Biophys. Acta 1761 (2006) 1506-1514
153. Takahashi N., Kawada T., Goto T., Yamamoto T., Taimatsu A., Matsui N., Kimura K., Saito M., Hosokawa M., Miyashita K., and Fushiki T. Dual action of isoprenols from herbal medicines on both PPARgamma and PPARalpha in 3T3-L1 adipocytes and HepG2 hepatocytes. FEBS Lett. 514 (2002) 315-322
154. Duncan R.E., and Archer M.C. Farnesol decreases serum triglycerides in rats: identification of mechanisms including up-regulation of PPARalpha and down-regulation of fatty acid synthase in hepatocytes. Lipids 43 (2008) 619-627
155. Hanley K., Jiang Y., Crumrine D., Bass N.M., Appel R., Elias P.M., Williams M.L., and Feingold K.R. Activators of the nuclear hormone receptors PPARalpha and FXR accelerate the development of the fetal epidermal permeability barrier. J. Clin. Invest. 100 (1997) 705-712
156. Hanley K., Komuves L.G., Bass N.M., He S.S., Jiang Y., Crumrine D., Appel R., Friedman M., Bettencourt J., Min K., Elias P.M., Williams M.L., and Feingold K.R. Fetal epidermal differentiation and barrier development in vivo is accelerated by nuclear hormone receptor activators. J. Invest. Dermatol. 113 (1999) 788-795
157. Jetten A.M., and Harvat B.L. Epidermal differentiation and squamous metaplasia: from stem cell to cell death. J. Dermatol. 24 (1997) 711-725
158. Duncan R.E., and Archer M.C. Farnesol induces thyroid hormone receptor (THR) beta1 but inhibits THR-mediated signaling in MCF-7 human breast cancer cells. Biochem. Biophys. Res. Commun. 343 (2006) 239-243
159. Hall L.C., Salazar E.P., Kane S.R., and Liu N. Effects of thyroid hormones on human breast cancer cell proliferation. J. Steroid Biochem. Mol. Biol. 109 (2008) 57-66
160. Martínez-Iglesias O., Garcia-Silva S., Tenbaum S.P., Regadera J., Larcher F., Paramio J.M., Vennström B., and Aranda A. Thyroid hormone receptor beta1 acts as a potent suppressor of tumor invasiveness and metastasis. Cancer Res. 69 (2009) 501-509