Cation-selective transporters are critical to the AMPK-mediated antiproliferative effects of metformin in human breast cancer cells: Transporters in metformin effect against breast cancer cells
Open accessAbstract
The antidiabetic drug metformin exerts antineoplastic effects against breast cancer and other cancers. One mechanism by which metformin is believed to exert its anticancer effect involves activation of its intracellular target, adenosine monophosphate-activated protein kinase (AMPK), which is also implicated in the antidiabetic effect of metformin. It is proposed that in cancer cells, AMPK activation leads to inhibition of the mammalian target of rapamycin (mTOR) and the downstream pS6K that regulates cell proliferation. Due to its hydrophilic and cationic nature, metformin requires cation-selective transporters to enter cells and activate AMPK. This study demonstrates that expression levels of cation-selective transporters correlate with the antiproliferative and antitumor efficacy of metformin in breast cancer. Metformin uptake and antiproliferative activity were compared between a cation-selective transporter-deficient human breast cancer cell line, BT-20, and a BT-20 cell line that was engineered to overexpress organic cation transporter 3 (OCT3), a representative of cation-selective transporters and a predominant transporter in human breast tumors. Metformin uptake was minimal in BT-20 cells, but increased by >13-fold in OCT3-BT20 cells, and its antiproliferative potency was >4-fold in OCT3-BT20 versus BT-20 cells. This increase in antiproliferative activity was associated with greater AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells. In vitro data were corroborated by in vivo observations of significantly greater antitumor efficacy of metformin in xenograft mice bearing OCT3-overexpressing tumors versus low transporter-expressing wildtype tumors. Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
[14C]-Metformin uptake was 13 times higher in OCT3-BT20 cells than in BT-20 cells, and associated with increased AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells, and these results were substantiated in mice with OCT3 overexpressing tumors.
“[14C]-Metformin uptake was 13 times higher in OCT3-BT20 cells than in BT-20 cells, and associated with increased AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells and these results were substantiated in mice with OCT3 overexpressing tumors (241).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [241]
A logical target whereby metformin could mediate its putative antiproliferative effects in cancer is via inhibition of mTOR and pS6K, either via activation of AMPK or via an AMPK-independent pathway.
“A logical target whereby metformin could mediate its putative antiproliferative effects in cancer is via inhibition of mTOR and the serine-threonine kinase, ribosomal S6K (pS6K), either via activation of AMPK or via an AMPK-independent pathway (241, 242).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [241]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950 · see citing works
LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650 · see citing works
Cheang, M. C. U., Voduc, D. K., Bajdik, C. D., Leung, S. C. Y., McKinney, S. E., Chia, S., Perou, C. M., & Nielsen, T. O. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1658 · Cited by 1,197 · see citing works
Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells
Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N., & Pollak, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1500 · Cited by 1,048 · see citing works
Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action
Shu, Y., Sheardown, S. A., Brown, C., Owen, R., Zhang, S., Castro, R. A., Ianculescu, A. G., Lin, Y., Lo, J. C.-M., Burchard, E. G., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30558 · Cited by 971 · see citing works
Dowling, R. J. O., Zakikhani, M., Fantus, I. G., Pollak, M., & Sonenberg, N. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2310 · Cited by 933 · see citing works
Jiralerspong, S., Palla, S. L., Giordano, S. H., Meric-Bernstam, F., Liedtke, C., Barnett, C. M., Hsu, L., Hung, M.-C., Hortobagyi, G. N., & Gonzalez-Angulo, A. M. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.19.6410 · Cited by 880 · cited 1× · see citing works
“chemotherapy for breast cancer versus diabetic patients not on metformin (8%) or nondiabetic patients (16%).(14) An asso-”
BackgroundDunnwald, L. K., Rossing, M. A., & Li, C. I. (2007) · Breast Cancer Research · doi:10.1186/bcr1639 · Cited by 787 · see citing works
Hilgendorf, C., Ahlin, G., Seithel‐Keuth, A., Artursson, P., Ungell, A.-L. B., & Karlsson, J. E. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.014902 · Cited by 583 · see citing works
Alimova, I. N., Liu, B., Fan, Z., Edgerton, S. M., Dillon, T., Lind, S. E., & Thor, A. D. (2009) · Cell Cycle · doi:10.4161/cc.8.6.7933 · Cited by 523 · see citing works
Triple-Negative Breast Cancer: Distinguishing between Basal and Nonbasal Subtypes
Rakha, E. A., Elsheikh, S. E., Aleskandarany, M. A., Habashi, H. O., Green, A. R., Powe, D. G., El‐Sayed, M. E., Benhasouna, A., Brunet, J., Akslen, L. A., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2132 · Cited by 490 · see citing works
Effect of Genetic Variation in the Organic Cation Transporter 1, OCT1, on Metformin Pharmacokinetics
Shu, Y., Brown, C., Castro, R. A., Shi, R., Lin, E., Owen, R., Sheardown, S., Yue, L., Burchard, E. G., Brett, C., et al. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100275 · Cited by 474 · see citing works
Long-Term Metformin Use Is Associated With Decreased Risk of Breast Cancer
Bodmer, M., Meier, C., Krähenbühl, S., Jick, S. S., & Meier, C. R. (2010) · Diabetes Care · doi:10.2337/dc09-1791 · Cited by 466 · see citing works
Iliopoulos, D., Hirsch, H. A., & Struhl, K. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3471 · Cited by 451 · see citing works
Kim, Y. D., Park, K.-G., Lee, Y.-S., Park, Y.-Y., Kim, D.-K., Nedumaran, B., Jang, W. G., Cho, W.-J., Ha, J., Lee, I.-K., et al. (2008) · Diabetes · doi:10.2337/db07-0381 · Cited by 422 · see citing works
The role of insulin receptors and IGF-I receptors in cancer and other diseases
Frasca, F., Pandini, G., Sciacca, L., PEZZINO, V., Squatrito, S., Belfiore, A., & Vigneri, R. (2008) · Archives of Physiology and Biochemistry · doi:10.1080/13813450801969715 · Cited by 408 · see citing works
Mortality After Incident Cancer in People With and Without Type 2 Diabetes
Currie, C. J., Poole, C., Jenkins‐Jones, S., Gale, E. A., Johnson, J. A., & Morgan, C. L. (2012) · Diabetes Care · doi:10.2337/dc11-1313 · Cited by 398 · see citing works
Nies, A. T., Koepsell, H., Winter, S., Burk, O., Klein, K., Kerb, R., Zanger, U. M., KEPPLER, D. O. R., Schwab, M. G., & Schaeffeler, E. (2009) · Hepatology · doi:10.1002/hep.23103 · Cited by 382 · see citing works
Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence
Xue, F., & Michels, K. B. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.3.823s · Cited by 352 · see citing works
cDNA Cloning and Functional Expression of a Novel Rat Kidney Organic Cation Transporter, OCT2
Okuda, M., Saito, H., Urakami, Y., Takano, M., & Inui, K. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1056 · Cited by 352 · see citing works
Hermann, L. S., Scherstén, B., Bitzén, P.-O., Kjellström, T., Lindgärde, F., & Melander, A. (1994) · Diabetes Care · doi:10.2337/diacare.17.10.1100 · Cited by 343 · see citing works
Hadad, S. M., Iwamoto, T., Jordan, L. B., Purdie, C. A., Bray, S. E., Baker, L., Jellema, G. L., Deharo, S., Hardie, D. G., Pusztai, L., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1612-1 · Cited by 293 · see citing works
Storozhuk, Y., Hopmans, S., Sanli, T., Barron, C. C., Tsiani, E., Cutz, J.-C., Pond, G. R., Wright, J. R., Singh, G., & Tsakiridis, T. K. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.187 · Cited by 272 · see citing works
Zhou, M., Li, X., & Wang, J. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015495 · Cited by 251 · see citing works
Chen, Y., Li, S., Brown, C., Cheatham, S. C., Castro, R. A., Leabman, M. K., Urban, T. J., Chen, L., Yee, S. W., Choi, J. H., et al. (2009) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32832cc7e9 · Cited by 249 · see citing works
The Antidiabetic Drug Metformin Inhibits Gastric Cancer Cell Proliferation In Vitro and In Vivo
Kato, K., Gong, J., Iwama, H., Kitanaka, A., Tani, J., Miyoshi, H., Nomura, K., Mimura, S., Kobayashi, M., Aritomo, Y., et al. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0594 · Cited by 225 · see citing works
Drug transport proteins in the liver
Faber, K. N., Müller, M. M., & Jansen, P. L. M. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00173-4 · Cited by 220 · see citing works
Tan, E. Y., Yan, M., Campo, L., Han, C., Takano, E. A., Turley, H., Candiloro, I. L. M., Pezzella, F., Gatter, K. C., Millar, E. K. A., et al. (2009) · British Journal of Cancer · doi:10.1038/sj.bjc.6604844 · Cited by 195 · see citing works
STOCKER, S. L., Morrissey, K. M., Yee, S. W., Castro, R. A., Xu, L., Dahlin, A., Ramirez, A. H., Roden, D. M., Wilke, R. A., McCarty, C. A., et al. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.210 · Cited by 193 · see citing works
Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor
Ish‐Shalom, D., Christoffersen, C. T., Vorwerk, P., Sacerdoti‐Sierra, N., Shymko, R. M., Naor, D., & MEYTS, P. D. (1997) · Diabetologia · doi:10.1007/s001250051393 · Cited by 193 · see citing works
Bayraktar, S., Hernadez‐Aya, L. F., Lei, X., Meric‐Bernstam, F., Litton, J. K., Hsu, L., Hortobagyi, G. N., & Gonzalez‐Angulo, A. M. (2012) · Cancer · doi:10.1002/cncr.26439 · Cited by 176 · see citing works
Association between diabetes mellitus and breast cancer risk: a meta-analysis of the literature.
Liao, S., Li, J., Wei, W., Wang, L., Zhang, Y., Li, J., Wang, C., & Sun, S. (2011) · PubMed · Cited by 164 · see citing works
Self-citationDiabetes increases the risk of breast cancer: a meta-analysis
Hardefeldt, P. J., Edirimanne, S., & Eslick, G. D. (2012) · Endocrine Related Cancer · doi:10.1530/erc-12-0242 · Cited by 164 · see citing works
The tumor suppressor gene LKB1 is associated with prognosis in human breast carcinoma.
Shen, Z., Wen, X. F., Lan, F., Shen, Z. Z., & Shao, Z. M. (2002) · PubMed · Cited by 138 · see citing works
Mechanisms Underlying Saturable Intestinal Absorption of Metformin
Proctor, W. R., Bourdet, D. L., & Thakker, D. R. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.020180 · Cited by 132 · see citing works
Self-citationHan, T. K., Proctor, W. R., Costales, C., Cai, H., Everett, R., & Thakker, D. R. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.220350 · Cited by 123 · see citing works
Self-citationDiabetes and Cancer: Is Diabetes Causally Related to Cancer?
Suh, S., & Kim, K. (2011) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2011.35.3.193 · Cited by 118 · see citing works
Zhuang, Y., & Miskimins, W. K. (2011) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-10-0343 · Cited by 109 · see citing works
Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer
Colquhoun, A., Venier, N. A., Vandersluis, A. D., Besla, R., Sugar, L., Kiss, A., Fleshner, N. E., Pollak, M., Klotz, L. H., & Venkateswaran, V. K. (2012) · Prostate Cancer and Prostatic Diseases · doi:10.1038/pcan.2012.16 · Cited by 103 · see citing works
McIntyre, D. H., Paterson, C. A., Ma, A., Ravenscroft, P. J., Bird, D., & Cameron, D. P. (1991) · Australian and New Zealand Journal of Medicine · doi:10.1111/j.1445-5994.1991.tb01375.x · Cited by 98 · see citing works
Détaille, D., Guigas, B., Leverve, X. M., Wiernsperger, N. F., & Devos, P. E. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)00858-4 · Cited by 97 · see citing works
Relevance of the OCT1 transporter to the antineoplastic effect of biguanides
Segal, E., Yasmeen, A., Beauchamp, M.-C., Rosenblatt, J., Pollak, M., & Gotlieb, W. H. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.09.134 · Cited by 90 · see citing works
Hermann, L. S., Scherstén, B., & Melander, A. (1994) · Diabetic Medicine · doi:10.1111/j.1464-5491.1994.tb00253.x · Cited by 87 · see citing works
Saitoh, R., Sugano, K., Takata, N., Tachibana, T., Higashida, A., Nabuchi, Y., & Aso, Y. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000026423.48583.e2 · Cited by 85 · see citing works
Chisamore, M. J., Wilkinson, H. A., Flores, O. A., & Chen, J. D. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-1028 · Cited by 78 · see citing works
Patel, H. Y., Younis, R. H., Ord, R. A., Basile, J. R., & Schneider, A. (2012) · Journal of Oral Pathology and Medicine · doi:10.1111/j.1600-0714.2012.01196.x · Cited by 35 · see citing works
Flagged first, then by citations
1 of the 47 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- V C 2015 UICC 10970215, 2016, 9, Transporters in metformin effect against breast cancer cells Int. J. Cancer: 138, 2281-2292 (2016) · DOI
- V C 2015 UICC 10970215, 2016, 9, · DOI
- V C 2015 UICC 10970215, 2016, 9, uptake and accumulation of metformin in caco-2 cell monolayers. J Pharmacol Exp Ther 2015; 352: 519-28. · DOI
- Segal ED, Yasmeen A, Beauchamp MC, et al. Relevance of theOCT1 transporter to the antineo- plastic effect of biguanides. Biochem Biophys Res Commun 2011; 414:694-9.
Cited by
Sorted by citations
Repurposing metformin for the prevention of cancer and cancer recurrence
Heckman‐Stoddard, B. M., DeCensi, A., Sahasrabuddhe, V. V., & Ford, L. G. (2017) · Diabetologia · doi:10.1007/s00125-017-4372-6 · Cited by 299 · see citing works
Organic Cation Transporters in Health and Disease
Koepsell, H. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.015578 · Cited by 293 · see citing works
Mohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278 · see citing works
Metformin: Is it a drug for all reasons and diseases?
Triggle, C. R., Mohammed, I., Bshesh, K., Marei, I., Ye, K., Ding, H., MacDonald, R. S., Hollenberg, M. D., & Hill, M. A. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155223 · Cited by 282 · see citing works
Emerging roles of aerobic glycolysis in breast cancer
Wu, Z., Wu, J., Zhao, Q., Fu, S., & Jin, J. (2019) · Clinical & Translational Oncology · doi:10.1007/s12094-019-02187-8 · Cited by 260 · see citing works
Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem cells
Saini, N., & Yang, X. (2017) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmx106 · Cited by 174 · see citing works
Effect of Liver Disease on Hepatic Transporter Expression and Function
Thakkar, N., Slizgi, J. R., & Brouwer, K. L. R. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.04.053 · Cited by 126 · see citing works
Hasanvand, A. (2022) · Inflammopharmacology · doi:10.1007/s10787-022-00980-6 · Cited by 105 · see citing works
RETRACTED: Metformin and Breast Cancer: Where Are We Now?
Solís, M. C., Martı́n-Castillo, B., Menéndez, J. A., & Pernas, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052705 · Cited by 85 · see citing works
RetractedSamuel, S., Varghese, E., Kubatka, P., Triggle, C., & Büsselberg, D. (2019) · Biomolecules · doi:10.3390/biom9120846 · Cited by 81 · see citing works
Metformin and Breast Cancer: Molecular Targets
Faria, J., Negalha, G. D. C., Azevedo, A., & Martel, F. (2019) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-019-09429-z · Cited by 75 · see citing works
Zhang, J., Li, G., Chen, Y., Fang, L., Chen, G., Bai, F., Ma, M., Lyu, J., & Meng, Q. H. (2017) · Journal of Cancer · doi:10.7150/jca.19858 · Cited by 58 · see citing works
Sutherland, R., Meeson, A. P., & Lowes, S. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09879-6 · Cited by 54 · see citing works
Counteracting Chemoresistance with Metformin in Breast Cancers: Targeting Cancer Stem Cells
Samuel, S. M., Varghese, E., Koklesová, L., Líšková, A., Kubatka, P., & Büsselberg, D. (2020) · Cancers · doi:10.3390/cancers12092482 · Cited by 53 · see citing works
Metformin: A Possible Option in Cancer Chemotherapy
Ugwueze, C. V., Ogamba, O. J., Young, E. E., Onyenekwe, B. M., & Ezeokpo, B. C. (2020) · Analytical Cellular Pathology · doi:10.1155/2020/7180923 · Cited by 52 · see citing works
Corleto, K. A., Strandmo, J. L., & Giles, E. D. (2024) · Pharmaceuticals · doi:10.3390/ph17030396 · Cited by 44 · see citing works
Checkley, L. A., Rudolph, M. C., Wellberg, E. A., Giles, E. D., Wahdan-Alaswad, R. S., Houck, J. A., Edgerton, S. M., Thor, A. D., Schedin, P., Anderson, S. M., et al. (2017) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-16-0211-t · Cited by 43 · see citing works
Jin, D., Guo, J., Wang, D., Wu, Y., Wang, X., Gao, Y., Shao, C., Xu, X., & Tan, S. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.10.044 · Cited by 39 · see citing works
RetractedPan, Y., Jiao, L., Lin, C., Lu, C., Li, L., Chen, H., Wang, Y., & He, Y. (2018) · Biologics · doi:10.2147/btt.s166867 · Cited by 34 · see citing works
MATE2 Expression Is Associated With Cancer Cell Response to Metformin
Chowdhury, S., Yung, E., Pintilie, M., Muaddi, H., Chaib, S., Yeung, M., Fusciello, M., Sykes, J., Pitcher, B., Hagenkort, A., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165214 · Cited by 33 · see citing works
Mathews Samuel, S., Satheesh, N. J., Ghosh, S., Büsselberg, D., Majeed, Y., Ding, H., & Triggle, C. R. (2019) · Cancers · doi:10.3390/cancers11111737 · Cited by 28 · see citing works
Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs
Gremke, N., Besong, I., Stroh, A., von Wichert, L., Witt, M., Elmshäuser, S., Wanzel, M., Fromm, M. F., Taudte, R. V., Schmatloch, S., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02180-4 · Cited by 28 · see citing works
Otter, M., Csader, S., Keiser, M., & Oswald, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010255 · Cited by 27 · see citing works
Cai, H., Everett, R. S., & Thakker, D. R. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14694 · Cited by 26 · see citing works
Self-citationFriedrich, S., Serbian, I., Hoenke, S., Wolfram, R. K., & Csük, R. (2020) · Medicinal Chemistry Research · doi:10.1007/s00044-020-02536-1 · Cited by 24 · see citing works
Markowicz-Piasecka, M., Huttunen, J., Sikora, J., & Huttunen, K. M. (2019) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2019.03.036 · Cited by 24 · see citing works
Cheng, G., Zielonka, J., Hardy, M., Ouari, O., Chitambar, C. R., Dwinell, M. B., & Kalyanaraman, B. (2019) · Oncotarget · doi:10.18632/oncotarget.26943 · Cited by 24 · see citing works
Cwynar-Zając, Ł. (2021) · Pediatric Endocrinology Diabetes and Metabolism · doi:10.5114/pedm.2021.107166 · Cited by 22 · see citing works
Ye, J., Qi, L., Chen, K., Li, R., Song, S., Zhou, C., & Zhai, W. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4820 · Cited by 20 · see citing works
Sciannimanico, S. M., Grimaldi, F., Vescini, F., Pergola, G. D., Iacoviello, M., Licchelli, B., Guastamacchia, E., Giagulli, V. A., & Triggiani, V. (2019) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530319666190507125847 · Cited by 20 · see citing works
Prognostic value of metformin in cancers: An updated meta-analysis based on 80 cohort studies
Yang, J., Yang, H., Cao, L., Yin, Y., Shen, Y., & Zhu, W. (2022) · Medicine · doi:10.1097/md.0000000000031799 · Cited by 16 · see citing works
Inhibition of organic cation transporter 3 activity by tyrosine kinase inhibitors
Alim, K., Moreau, A., Bruyère, A., Jouan, E., Denizot, C., Nies, A. T., Parmentier, Y., & Fardel, O. (2021) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12657 · Cited by 14 · see citing works
Markowicz-Piasecka, M., Huttunen, J., Zajda, A., Sikora, J., & Huttunen, K. M. (2021) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2021.109795 · Cited by 14 · see citing works
Gu, Z., Lin, S., Yan, W., Chen, D., Zeng, Z., Chen, L., Li, Y., & He, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113291 · Cited by 13 · see citing works
Markowicz-Piasecka, M., Sadowski, K., Huttunen, J., Sikora, J., & Huttunen, K. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115642 · Cited by 12 · see citing works
Samuel, S. M., Varghese, E., Satheesh, N. J., Triggle, C. R., & Büsselberg, D. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114911 · Cited by 11 · see citing works
Old Drug, New Science: Metformin and the Future of Pharmaceutics
Caturano, A., Nilo, D., Nilo, R., Sircana, M. C., Erul, E., Zielińska, K., Russo, V., Santonastaso, E., & Sasso, F. C. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18010077 · Cited by 8 · see citing works
Hassan, F. E., Aboulhoda, B. E., Mehesen, M. N., Mohie, P. M., Abdallah, H. A., Bendas, E. R., Rashed, L. A., Mostafa, A., Amer, M. F., Abdel-Rahman, M. M., et al. (2024) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2024.2407547 · Cited by 8 · see citing works
Sundelin, E. I. O., Al-Suliman, N. N., Vahl, P., Vendelbo, M. H., Munk, O. L., Jakobsen, S., Pedersen, S. B., Frøkiær, J., Gormsen, L. C., & Jessen, N. (2020) · Breast Cancer Research and Treatment · doi:10.1007/s10549-020-05621-6 · Cited by 8 · see citing works
Markowicz-Piasecka, M., Komeil, I. A., Huttunen, J., Sikora, J., & Huttunen, K. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072389 · Cited by 8 · see citing works
Metformin as a Potential In Vitro Anticancer Modulator of Adenosine Monophosphate Kinase: A Review
Jinadasa, A. G. R. G., Akalanka, H. M. K., Wageesha, N. D. A., & Ekanayake, S. (2024) · International Journal of Breast Cancer · doi:10.1155/2024/1094274 · Cited by 3 · see citing works
Alipour, S., Rastad, H., Saberi, A., Faiz, F., Maleki‐Hajiagha, A., & Abedi, M. (2021) · DARU Journal of Pharmaceutical Sciences · doi:10.1007/s40199-021-00424-6 · Cited by 3 · see citing works
Kuorikoski, V., Tampio, J., Kerachni, S., Timonen, D., Tonduru, A. K., Markowicz-Piasecka, M., Terasaki, T., Poso, A., & Huttunen, K. M. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5c00432 · Cited by 2 · see citing works
Design and optimization of metformin solid lipid microparticles for topical application
Mancer, D., Agouillal, F., & Daoud, K. (2024) · European Journal of Lipid Science and Technology · doi:10.1002/ejlt.202300221 · Cited by 1 · see citing works
Sutherland, R., Meeson, A. P., & Lowes, S. (2021) · Research Square · doi:10.21203/rs.3.rs-349903/v1 · Cited by 1 · see citing works
Metformin as Adjuvant Therapy in Ovarian and Endometrial Cancers
Clark, L. H., & Bae-Jump, V. L. (2017) · Energy balance and cancer · doi:10.1007/978-3-319-63483-8_16
- Authors
- Cai, H., Zhang, Y., Han, T. K., Everett, R. S., & Thakker, D. R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Thakker, Dhiren R.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2016-01-08
- Volume
- 138
- Issue
- 9
- Pages
- 2281-2292
- ISSN
- 0020-7136 (ISSN-L)
- OpenAlex
- W2220293484
- Cited by
- 46
- References
- 47
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 2 · 2017: 6 · 2016: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- North Carolina Translational Clinical Research Sciences Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- metformin, OCT3, breast cancer, AMPK activation, mTOR signaling, drug uptake, antiproliferative activity, anticancer drug repurposing, tumor xenografts
- MeSH terms
- Organic Cation Transporter 3, Animals, Antineoplastic Agents, Breast Neoplasms, Female, Mammary Neoplasms, Experimental, Metformin, Mice, Nude, Signal Transduction, Xenograft Model Antitumor Assays, Organic Cation Transport Proteins, Ribosomal Protein S6 Kinases, 70-kDa, Cell Line, Tumor, Cell Proliferation, Mice, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
