Cation-selective transporters are critical to the AMPK-mediated antiproliferative effects of metformin in human breast cancer cells

International Journal of Cancer

Volumn 138, Issue 9, 2016, Pages 2281-2292

  Cai, Hao ^a   Zhang, Yunhui ^a,b   Han, Tianxiang ^a   Everett, Ruth S ^a   Thakker, Dhiren R ^a  

^a UNC Hamner Institute for Drug Safety Sciences   (United States)

^b JILIN UNIVERSITY   (China)

Author keywords

AMPK pathway; antiproliferative activity; breast cancer; metformin; transporters

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MAMMALIAN TARGET OF RAPAMYCIN; METFORMIN; ORGANIC CATION TRANSPORTER 3; S6 KINASE; ANTINEOPLASTIC AGENT; MTOR PROTEIN, HUMAN; ORGANIC CATION TRANSPORTER; SOLUTE CARRIER FAMILY 22 (ORGANIC CATION TRANSPORTER), MEMBER 3; TARGET OF RAPAMYCIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BIOENGINEERING; BREAST CANCER; BREAST CANCER CELL LINE; BT 20 CELL LINE; CANCER CELL; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; DRUG UPTAKE; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; ANIMAL; BREAST TUMOR; CELL PROLIFERATION; DRUG EFFECTS; DRUG SCREENING; FEMALE; MAMMARY NEOPLASMS, EXPERIMENTAL; METABOLISM; NUDE MOUSE; PATHOLOGY; TUMOR CELL LINE;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; FEMALE; MAMMARY NEOPLASMS, EXPERIMENTAL; METFORMIN; MICE; MICE, NUDE; ORGANIC CATION TRANSPORT PROTEINS; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84958864985     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.29965     Document Type: Article

References (47)

1. American Cancer Society. Cancer facts & figures. Atlanta, GA: The Society, 2015. v.
2. Liao S, Li J, Wei W, et al., Association between diabetes mellitus and breast cancer risk: a meta-analysis of the literature. Asian Pac J Cancer Prev 2011; 12: 1061-5.
3. Xue F, Michels KB., Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence. The American Journal of Clinical nutrition 2007; 86: s823-35.
4. Suh S, Kim KW., Diabetes and cancer: is diabetes causally related to cancer? Diabetes Metab J 2011; 35: 193-8.
5. Hardefeldt PJ, Edirimanne S, Eslick GD., Diabetes increases the risk of breast cancer: a meta-analysis. Endocr Relat Cancer 2012; 19: 793-803.
6. Iliopoulos D, Hirsch HA, Struhl K., Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types. Cancer Res 2011; 71: 3196-201.
7. Colquhoun AJ, Venier NA, Vandersluis AD, et al., Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer. Prostate Cancer Prostatic Dis 2012; 15: 346-52.
8. Kato K, Gong J, Iwama H, et al., The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol Cancer Ther 2012; 11: 549-60.
9. Storozhuk Y, Hopmans SN, Sanli T, et al., Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer 2013; 108: 2021-3.
10. Alimova IN, Liu B, Fan Z, et al., Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle 2009; 8: 909-15.
11. Hadad S, Coates P, Jordan LB, et al., Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 2011; 128: 783-94.
12. Bodmer M, Meier C, Krahenbuhl S, et al., Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care 2010; 33: 1304-8.
13. Bayraktar S, Hernadez-Aya LF, Lei X, et al., Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer 2012; 118: 1202-11.
14. Jiralerspong S, Palla SL, Giordano SH, et al., Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 2009; 27: 3297-302.
15. Currie CJ, Poole CD, Jenkins-Jones S, et al., Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care 2012; 35: 299-30.
16. Ish-Shalom D, Christoffersen CT, Vorwerk P, et al., Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor. Diabetologia 1997; 40 Suppl 2: S25-31.
17. Frasca F, Pandini G, Sciacca L, et al., The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem 2008; 114: 23-37.
18. Zakikhani M, Dowling R, Fantus IG, et al., Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 2006; 66: 10269-73.
19. Dowling RJ, Zakikhani M, Fantus IG, et al., Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res 2007; 67: 10804-12.
20. Shaw RJ, Lamia KA, Vasquez D, et al., The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 2005; 310: 1642-6.
21. Kim YD, Park KG, Lee YS, et al., Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diabetes 2008; 57: 306-14.
22. McIntyre HD, Ma A, Bird DM, et al., Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus. Aust New Zeal J Med 1991; 21: 714-9.
23. Saitoh R, Sugano K, Takata N, et al., Correction of permeability with pore radius of tight junctions in Caco-2 monolayers improves the prediction of the dose fraction of hydrophilic drugs absorbed by humans. Pharm Res 2004; 21: 749-55.
24. Detaille D, Guigas B, Leverve X, et al., Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function. Biochem Pharmacol 2002; 63: 1259-72.
25. Hilgendorf C, Ahlin G, Seithel A, et al., Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos 2007; 35: 1333-40.
26. Zhou M, Xia L, Wang J., Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab Dispos 2007; 35: 1956-62.
27. Han TK, Proctor WR, Costales CL, et al., Four cation-selective transporters contribute to apical uptake and accumulation of metformin in caco-2 cell monolayers. J Pharmacol Exp Ther 2015; 352: 519-28.
28. Nies AT, Koepsell H, Winter S, et al., Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology 2009; 50: 1227-40.
29. Faber KN, Muller M, Jansen PL., Drug transport proteins in the liver. Adv Drug Deliv Rev 2003; 55: 107-24.
30. Okuda M, Saito H, Urakami Y, et al., cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2. Biochem Biophys Res Commun 1996; 224: 500-7.
31. Dunnwald LK, Rossing MA, Li CI., Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 2007; 9: R6
32. Cheang MC, Voduc D, Bajdik C, et al., Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 2008; 14: 1368-76.
33. Rakha EA, Elsheikh SE, Aleskandarany MA, et al., Triple-negative breast cancer: distinguishing between basal and nonbasal subtypes. Clin Cancer Res 2009; 15: 2302-10.
34. Tan EY, Yan M, Campo L, et al., The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy. Br J Cancer 2009; 100: 405-11.
35. Shen Z, Wen XF, Lan F, et al., The tumor suppressor gene LKB1 is associated with prognosis in human breast carcinoma. Clin Cancer Res 2002; 8: 2085-9.
36. Woods A, Johnstone SR, Dickerson K, et al., LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003; 13: 2004-8.
37. Zhuang Y, Miskimins WK., Metformin induces both caspase-dependent and poly(ADP-ribose) polymerase-dependent cell death in breast cancer cells. Mol Cancer Res MCR 2011; 9: 603-15.
38. Proctor WR, Bourdet DL, Thakker DR., Mechanisms underlying saturable intestinal absorption of metformin. Drug Metab Dispos 2008; 36: 1650-8.
39. Shu Y, Sheardown SA, Brown C, et al., Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 2007; 117: 1422-31.
40. Patel H, Younis RH, Ord RA, et al., Differential expression of organic cation transporter OCT-3 in oral premalignant and malignant lesions: potential implications in the antineoplastic effects of metformin. J Oral Pathol Med 2013; 42: 250-6.
41. Shu Y, Brown C, Castro RA, et al., Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther 2008; 83: 273-80.
42. Segal ED, Yasmeen A, Beauchamp MC, et al., Relevance of theOCT1 transporter to the antineoplastic effect of biguanides. Biochem Biophys Res Commun 2011; 414: 694-9.
43. Chisamore MJ, Wilkinson HA, Flores O, et al., Estrogen-related receptor-alpha antagonist inhibits both estrogen receptor-positive and estrogen receptor-negative breast tumor growth in mouse xenografts. Mol Cancer Ther 2009; 8: 672-81.
44. Stocker SL, Morrissey KM, Yee SW, et al., The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin. Clin Pharmacol Ther 2013; 93: 186-94.
45. Chen Y, Li S, Brown C, et al., Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet Genomics 2009; 19: 497-504.
46. Hermann LS, Schersten B, Melander A., Antihyperglycaemic efficacy, response prediction and dose-response relations of treatment with metformin and sulphonylurea, alone and in primary combination. Diabet Med 1994; 11: 953-60.
47. Hermann LS, Schersten B, Bitzen PO, et al., Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double-blind controlled study. Diabetes Care 1994; 17: 1100-9.