Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways

Akagi, 2005, Cytoprotective effects of heme oxygenase in acute renal failure, Contrib. Nephrol., 148, 70, 10.1159/000086044 Alaoui-Jamali, 2009, A novel experimental heme oxygenase-1-targeted therapy for hormone-refractory prostate cancer, Cancer Res., 69, 8017, 10.1158/0008-5472.CAN-09-0419 Banerjee, 2011, The heme oxygenase-1 protein is overexpressed in human renal cancer cells following activation of the Ras-Raf-ERK pathway and mediates anti-apoptotic signal, J. Biol. Chem., 286, 33580, 10.1074/jbc.M111.248401 Ben Sahra, 2011, Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1, Cancer Res., 71, 4366, 10.1158/0008-5472.CAN-10-1769 Berberat, 2005, Inhibition of heme oxygenase-1 increases responsiveness of pancreatic cancer cells to anticancer treatment, Clin. Cancer Res., 11, 3790, 10.1158/1078-0432.CCR-04-2159 Bhalla, 2012, Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis, Cancer Prev. Res. (Phila.), 5, 544, 10.1158/1940-6207.CAPR-11-0228 Bowker, 2006, Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin, Diabetes Care, 29, 254, 10.2337/diacare.29.02.06.dc05-1558 DeNicola, 2011, Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis, Nature, 475, 106, 10.1038/nature10189 Donadon, 2009, Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease, World J. Gastroenterol., 15, 2506, 10.3748/wjg.15.2506 Donadon, 2010, Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease, Liver Int., 30, 750, 10.1111/j.1478-3231.2010.02223.x Evans, 2005, Metformin and reduced risk of cancer in diabetic patients, BMJ, 330, 1304, 10.1136/bmj.38415.708634.F7 Fang, 2004, Antiapoptotic role of heme oxygenase (HO) and the potential of HO as a target in anticancer treatment, Apoptosis, 9, 27, 10.1023/B:APPT.0000012119.83734.4e Fang, 2009, Therapeutic strategies by modulating oxygen stress in cancer and inflammation, Adv. Drug Deliv. Rev., 61, 290, 10.1016/j.addr.2009.02.005 Hirai, 2007, Inhibition of heme oxygenase-1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice, Int. J. Cancer, 120, 500, 10.1002/ijc.22287 Hwang, 2010, Br. J. Pharmacol., 160, 1195, 10.1111/j.1476-5381.2010.00762.x Jozkowicz, 2007, Heme oxygenase-1 in tumors: is it a false friend?, Antioxid. Redox Signal., 9, 2099, 10.1089/ars.2007.1659 Kim, 2011, Metformin inhibits P-glycoprotein expression via the NF-kappaB pathway and CRE transcriptional activity through AMPK activation, Br. J. Pharmacol., 162, 1096, 10.1111/j.1476-5381.2010.01101.x Kobayashi, 2005, Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation, Antioxid. Redox Signal., 7, 385, 10.1089/ars.2005.7.385 Kobayashi, 2006, Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1, Mol. Cell. Biol., 26, 221, 10.1128/MCB.26.1.221-229.2006 Kongpetch, 2012, Crucial role of heme oxygenase-1 on the sensitivity of cholangiocarcinoma cells to chemotherapeutic agents, PLoS One, 7, e34994, 10.1371/journal.pone.0034994 Kwak, 2002, Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter, Mol. Cell. Biol., 22, 2883, 10.1128/MCB.22.9.2883-2892.2002 Kweon, 2006, Constitutive overexpression of Nrf2-dependent heme oxygenase-1 in A549 cells contributes to resistance to apoptosis induced by epigallocatechin 3-gallate, J. Biol. Chem., 281, 33761, 10.1074/jbc.M604748200 Lee, 2005, Nrf2 as a novel molecular target for chemoprevention, Cancer Lett., 224, 171, 10.1016/j.canlet.2004.09.042 Lee, 2003, AMP-activated protein kinase activity is critical for hypoxia-inducible factor-1 transcriptional activity and its target gene expression under hypoxic conditions in DU145 cells, J. Biol. Chem., 278, 39653, 10.1074/jbc.M306104200 Liu, 2004, Upregulation of heme oxygenase-1 and p21 confers resistance to apoptosis in human gastric cancer cells, Oncogene, 23, 503, 10.1038/sj.onc.1207173 Martin, 2004, Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol, J. Biol. Chem., 279, 8919, 10.1074/jbc.M309660200 Miyake, 2011, Heme oxygenase-1 promotes angiogenesis in urothelial carcinoma of the urinary bladder, Oncol. Rep., 25, 653, 10.3892/or.2010.1125 Nguyen, 2003, Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26S proteasome, J. Biol. Chem., 278, 4536, 10.1074/jbc.M207293200 Nuhn, 2009, Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivo, Mol. Cancer, 8, 37, 10.1186/1476-4598-8-37 Ohta, 2008, Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth, Cancer Res., 68, 1303, 10.1158/0008-5472.CAN-07-5003 Omerovic, 2008, Ras isoform abundance and signalling in human cancer cell lines, Oncogene, 27, 2754, 10.1038/sj.onc.1210925 Ren, 2011, Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism, Proc. Natl. Acad. Sci. U. S. A., 108, 1433, 10.1073/pnas.1014275108 Sadeghi, 2012, Metformin use is associated with better survival of diabetic patients with pancreatic cancer, Clin. Cancer Res., 18, 2905, 10.1158/1078-0432.CCR-11-2994 Sass, 2008, Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice, Int. J. Cancer, 123, 1269, 10.1002/ijc.23695 Shaw, 2005, The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin, Science, 310, 1642, 10.1126/science.1120781 Shibata, 2008, Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy, Proc. Natl. Acad. Sci. U. S. A., 105, 13568, 10.1073/pnas.0806268105 Singh, 2008, RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy, Cancer Res., 68, 7975, 10.1158/0008-5472.CAN-08-1401 Spicer, 2003, Regulation of the Wnt signalling component PAR1A by the Peutz–Jeghers syndrome kinase LKB1, Oncogene, 22, 4752, 10.1038/sj.onc.1206669 Sunamura, 2003, Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer, Angiogenesis, 6, 15, 10.1023/A:1025803600840 Tang, 2011, Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs, Free Radic. Biol. Med., 50, 1599, 10.1016/j.freeradbiomed.2011.03.008 Tiainen, 1999, Growth suppression by Lkb1 is mediated by a G(1) cell cycle arrest, Proc. Natl. Acad. Sci. U. S. A., 96, 9248, 10.1073/pnas.96.16.9248 Vitale-Cross, 2012, Metformin prevents the development of oral squamous cell carcinomas from carcinogen-induced premalignant lesions, Cancer Prev. Res. (Phila.), 5, 562, 10.1158/1940-6207.CAPR-11-0502 Wagener, 2001, Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase, Blood, 98, 1802, 10.1182/blood.V98.6.1802 Wang, 2008, Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2, Carcinogenesis, 29, 1235, 10.1093/carcin/bgn095 Was, 2010, Heme oxygenase-1 in tumor biology and therapy, Curr. Drug Targets, 11, 1551, 10.2174/1389450111009011551 Xiao, 2012, Metformin impairs the growth of liver kinase B1-intact cervical cancer cells, Gynecol. Oncol., 127, 249, 10.1016/j.ygyno.2012.06.032 Zakikhani, 2006, Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells, Cancer Res., 66, 10269, 10.1158/0008-5472.CAN-06-1500