Progress in antitumor mechanisms and applications of phenformin (Review)
- Authors:
- Qi Zhong
- Duo Li
- Xiao-Ping Yang
-
Affiliations: Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, P.R. China - Published online on: September 13, 2024 https://doi.org/10.3892/or.2024.8810
- Article Number: 151
-
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
 |
 |
|
Liu J, Zhang M, Deng D and Zhu X: The function, mechanisms, and clinical applications of metformin: Potential drug, unlimited potentials. Arch Pharm Res. 46:389–407. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, Ligibel JA, Hershman DL, Mayer IA, Hobday TJ, et al: Effect of metformin vs. placebo on invasive Disease-Free survival in patients with breast cancer: The MA.32 randomized clinical trial. JAMA. 327:1963–1973. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Galal MA, Al-Rimawi M, Hajeer A, Dahman H, Alouch S and Aljada A: Metformin: A Dual-role player in cancer treatment and prevention. Int J Mol Sci. 25:40832024. View Article : Google Scholar : PubMed/NCBI | |
|
García Rubiño ME, Carrillo E, Ruiz Alcalá G, Domínguez-Martín A, A Marchal J and Boulaiz H: Phenformin as an anticancer agent: Challenges and prospects. Int J Mol Sci. 20:33162019. View Article : Google Scholar : PubMed/NCBI | |
|
Bridges HR, Blaza JN, Yin Z, Chung I, Pollak MN and Hirst J: Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides. Science. 379:351–357. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Yuan P, Ito K, Perez-Lorenzo R, Del Guzzo C, Lee JH, Shen CH, Bosenberg MW, McMahon M, Cantley LC and Zheng B: Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. Proc Natl Acad Sci USA. 110:18226–18231. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao H, Swanson KD and Zheng B: Therapeutic repurposing of biguanides in cancer. Trends Cancer. 7:714–730. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Di Magno L, Manni S, Di Pastena F, Coni S, Macone A, Cairoli S, Sambucci M, Infante P, Moretti M, Petroni M, et al: Phenformin inhibits Hedgehog-dependent tumor growth through a Complex I-independent redox/corepressor module. Cell Rep. 30:1735–1752.e7. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Kalender A, Selvaraj A, Kim SY, Gulati P, Brûlé S, Viollet B, Kemp BE, Bardeesy N, Dennis P, Schlager JJ, et al: Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 11:390–401. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Kim SH, Li M, Trousil S, Zhang Y, Pasca di Magliano M, Swanson KD and Zheng B: Phenformin inhibits Myeloid-derived suppressor cells and enhances the Anti-tumor activity of PD-1 blockade in melanoma. J Invest Dermatol. 137:1740–1748. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhuang D, Wang S, Liu G, Liu P, Deng H, Sun J, Liu C, Leng X, Zhang Q, Bai F, et al: Phenformin suppresses angiogenesis through the regulation of exosomal microRNA-1246 and microRNA-205 levels derived from oral squamous cell carcinoma cells. Front Oncol. 12:9434772022. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang W, Finniss S, Cazacu S, Xiang C, Brodie Z, Mikkelsen T, Poisson L, Shackelford DB and Brodie C: Repurposing phenformin for the targeting of glioma stem cells and the treatment of glioblastoma. Oncotarget. 7:56456–56470. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhuang D, Wang S, Deng H, Shi Y, Liu C, Leng X, Zhang Q, Bai F, Zheng B, Guo J, et al: Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK. Int J Oral Sci. 16:352024. View Article : Google Scholar : PubMed/NCBI | |
|
Nussinov R, Tsai CJ and Jang H: Anticancer drug resistance: An update and perspective. Drug Resist Updat. 59:1007962021. View Article : Google Scholar : PubMed/NCBI | |
|
Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, Yang W, Tian C, Miao Z, Wang T, et al: Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Signal Transduct Target Ther. 6:2012021. View Article : Google Scholar : PubMed/NCBI | |
|
Lee S, Lee JS, Seo J, Lee SH, Kang JH, Song J and Kim SY: Targeting mitochondrial oxidative phosphorylation abrogated irinotecan resistance in NSCLC. Sci Rep. 8:157072018. View Article : Google Scholar : PubMed/NCBI | |
|
Peng M, Deng J, Zhou S, Xiao D, Long J, Zhang N, He C, Mo M and Yang X: Dual inhibition of Pirarubicin-induced AKT and ERK activations by phenformin sensitively suppresses bladder cancer growth. Front Pharmacol. 10:11592019. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Xia S and Zhu Z: Synergistic effect of phenformin in non-small cell lung cancer (NSCLC) ionizing radiation treatment. Cell Biochem Biophys. 71:513–518. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Martin MJ, Eberlein C, Taylor M, Ashton S, Robinson D and Cross D: Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma. Oncotarget. 7:86313–86325. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Huang L, Xiao D, Wu T, Hu X, Deng J, Yan X, Wu J, Xu S, Yang X and Li G: Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways. Am J Transl Res. 13:7508–7523. 2021.PubMed/NCBI | |
|
Chapman PB, Klang M, Postow MA, Shoushtari AN, Sullivan RJ, Wolchok JD, Merghoub T, Budhu S, Wong P, Callahan MK, et al: Phase Ib trial of phenformin in patients with V600-mutated melanoma receiving dabrafenib and trametinib. Cancer Res Commun. 3:2447–2454. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Nattrass M and Alberti KG: Biguanides. Diabetologia. 14:71–74. 1978. View Article : Google Scholar : PubMed/NCBI | |
|
Stang M, Wysowski DK and Butler-Jones D: Incidence of lactic acidosis in metformin users. Diabetes Care. 22:925–927. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Lea MA, Chacko J, Bolikal S, Hong JY, Chung R, Ortega A and Desbordes C: Addition of 2-deoxyglucose enhances growth inhibition but reverses acidification in colon cancer cells treated with phenformin. Anticancer Res. 31:421–426. 2011.PubMed/NCBI | |
|
Altinoz MA and Ozpinar A: Oxamate targeting aggressive cancers with special emphasis to brain tumors. Biomed Pharmacother. 147:1126862022. View Article : Google Scholar : PubMed/NCBI | |
|
Appleyard MV, Murray KE, Coates PJ, Wullschleger S, Bray SE, Kernohan NM, Fleming S, Alessi DR and Thompson AM: Phenformin as prophylaxis and therapy in breast cancer xenografts. Br J Cancer. 106:1117–1122. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Chowdhury TA: Diabetes and cancer. QJM. 103:905–915. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Anari F, Ramamurthy C and Zibelman M: Impact of tumor microenvironment composition on therapeutic responses and clinical outcomes in cancer. Future Oncol. 14:1409–1421. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kim HJ, Ji YR and Lee YM: Crosstalk between angiogenesis and immune regulation in the tumor microenvironment. Arch Pharm Res. 45:401–416. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Gabrilovich DI: Myeloid-derived suppressor cells. Cancer Immunol Res. 5:3–8. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Toh B, Wang X, Keeble J, Sim WJ, Khoo K, Wong WC, Kato M, Prevost-Blondel A, Thiery JP and Abastado JP: Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol. 9:e10011622011. View Article : Google Scholar : PubMed/NCBI | |
|
Shrihari GT: Innate and adaptive immune cells in Tumor microenvironment. Gulf J Oncolog. 1:77–81. 2021. | |
|
Li Q and Xiang M: Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy. Acta Pharmacol Sin. 43:1337–1348. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Mathieu M, Martin-Jaular L, Lavieu G and Théry C: Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 21:9–17. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Tkach M and Théry C: Communication by extracellular vesicles: Where we are and where we need to go. Cell. 164:1226–1232. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao Y, Dong Q, Li J, Zhang K, Qin J, Zhao J, Sun Q, Wang Z, Wartmann T, Jauch KW, et al: Targeting cancer stem cells and their niche: Perspectives for future therapeutic targets and strategies. Semin Cancer Biol. 53:139–155. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Petrachi T, Romagnani A, Albini A, Longo C, Argenziano G, Grisendi G, Dominici M, Ciarrocchi A and Dallaglio K: Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma. Oncotarget. 8:6914–6928. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Luo Y, Dallaglio K, Chen Y, Robinson WA, Robinson SE, McCarter MD, Wang J, Gonzalez R, Thompson DC, Norris DA, et al: ALDH1A isozymes are markers of human melanoma stem cells and potential therapeutic targets. Stem Cells. 30:2100–2113. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Sarvi S, Crispin R, Lu Y, Zeng L, Hurley TD, Houston DR, von Kriegsheim A, Chen CH, Mochly-Rosen D, Ranzani M, et al: ALDH1 Bio-activates nifuroxazide to eradicate ALDH(High) Melanoma-Initiating cells. Cell Chem Biol. 25:1456–1469.e6. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kültz D: Molecular and evolutionary basis of the cellular stress response. Annu Rev Physiol. 67:225–257. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Xiao W, Wang RS, Handy DE and Loscalzo J: NAD(H) and NADP(H) redox couples and cellular energy metabolism. Antioxid Redox Signal. 28:251–272. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Contenti J, Guo Y, Mazzu A, Irondelle M, Rouleau M, Lago C, Leva G, Tiberi L, Ben-Sahra I, Bost F, et al: The mitochondrial NADH shuttle system is a targetable vulnerability for Group 3 medulloblastoma in a hypoxic microenvironment. Cell Death Dis. 14:7842023. View Article : Google Scholar : PubMed/NCBI | |
|
Kim S, Im JH, Kim WK, Choi YJ, Lee JY, Kim SK, Kim SJ, Kwon SW and Kang KW: Enhanced sensitivity of nonsmall cell lung cancer with acquired resistance to epidermal growth factor Receptor-Tyrosine kinase inhibitors to phenformin: The roles of a metabolic shift to oxidative phosphorylation and redox balance. Oxid Med Cell Longev. 2021:54283642021. View Article : Google Scholar : PubMed/NCBI | |
|
Cui Q, Wang JQ, Assaraf YG, Ren L, Gupta P, Wei L, Ashby CR Jr, Yang DH and Chen ZS: Modulating ROS to overcome multidrug resistance in cancer. Drug Resist Updat. 41:1–25. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Moloney JN and Cotter TG: ROS signalling in the biology of cancer. Semin Cell Dev Biol. 80:50–64. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Miskimins WK, Ahn HJ, Kim JY, Ryu S, Jung YS and Choi JY: Synergistic anti-cancer effect of phenformin and oxamate. PLoS One. 9:e855762014. View Article : Google Scholar : PubMed/NCBI | |
|
Totten SP, Im YK, Cepeda Cañedo E, Najyb O, Nguyen A, Hébert S, Ahn R, Lewis K, Lebeau B, La Selva R, et al: STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer. Nat Commun. 12:32992021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Meng Y, Zhang S, Wu H, Yang D, Nie C and Hu Q: Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo. Onco Targets Ther. 11:6039–6048. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Di Conza G and Ho PC: ER Stress responses: An emerging modulator for innate immunity. Cells. 9:6952020. View Article : Google Scholar : PubMed/NCBI | |
|
Cubillos-Ruiz JR, Bettigole SE and Glimcher LH: Tumorigenic and immunosuppressive effects of endoplasmic reticulum stress in cancer. Cell. 168:692–706. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Cairns RA, Harris IS and Mak TW: Regulation of cancer cell metabolism. Nat Rev Cancer. 11:85–95. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng C, Geng F, Cheng X and Guo D: Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun (Lond). 38:272018.PubMed/NCBI | |
|
Laplante M and Sabatini DM: mTOR signaling in growth control and disease. Cell. 149:274–293. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Kim YC and Guan KL: mTOR: A pharmacologic target for autophagy regulation. J Clin Invest. 125:25–32. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Q, Liu S, Zhai A, Zhang B and Tian G: AMPK-Mediated regulation of lipid metabolism by phosphorylation. Biol Pharm Bull. 41:985–993. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Jackson AL, Sun W, Kilgore J, Guo H, Fang Z, Yin Y, Jones HM, Gilliam TP, Zhou C and Bae-Jump VL: Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer. Oncotarget. 8:100113–100127. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Lettieri Barbato D, Vegliante R, Desideri E and Ciriolo MR: Managing lipid metabolism in proliferating cells: New perspective for metformin usage in cancer therapy. Biochim Biophys Acta. 1845:317–324. 2014.PubMed/NCBI | |
|
Khan H, Anshu A, Prasad A, Roy S, Jeffery J, Kittipongdaja W, Yang DT and Schieke SM: Metabolic rewiring in response to biguanides is mediated by mROS/HIF-1a in malignant lymphocytes. Cell Rep. 29:3009–3018.e4. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Masoud R, Reyes-Castellanos G, Lac S, Garcia J, Dou S, Shintu L, Abdel Hadi N, Gicquel T, El Kaoutari A, Diémé B, et al: Targeting mitochondrial complex I overcomes chemoresistance in high OXPHOS pancreatic cancer. Cell Rep Med. 17:1001432020. View Article : Google Scholar : PubMed/NCBI | |
|
Bridges HR, Sirviö VA, Agip AN and Hirst J: Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase. BMC Biol. 14:652016. View Article : Google Scholar : PubMed/NCBI | |
|
Shackelford DB, Abt E, Gerken L, Vasquez DS, Seki A, Leblanc M, Wei L, Fishbein MC, Czernin J, Mischel PS and Shaw RJ: LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer Cell. 23:143–158. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Momcilovic M, McMickle R, Abt E, Seki A, Simko SA, Magyar C, Stout DB, Fishbein MC, Walser TC, Dubinett SM and Shackelford DB: Heightening energetic stress selectively targets LKB1-Deficient non-small cell lung cancers. Cancer Res. 75:4910–4922. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Izreig S, Gariepy A, Kaymak I, Bridges HR, Donayo AO, Bridon G, DeCamp LM, Kitchen-Goosen SM, Avizonis D, Sheldon RD, et al: Repression of LKB1 by miR-17~92 Sensitizes MYC-Dependent lymphoma to biguanide treatment. Cell Rep Med. 1:1000142020. View Article : Google Scholar : PubMed/NCBI | |
|
Hardie DG and Alessi DR: LKB1 and AMPK and the cancer-metabolism link-ten years after. BMC Biol. 11:362013. View Article : Google Scholar : PubMed/NCBI | |
|
Dalton KM, Lochmann TL, Floros KV, Calbert ML, Kurupi R, Stein GT, McClanaghan J, Murchie E, Egan RK, Greninger P, et al: Catastrophic ATP loss underlies a metabolic combination therapy tailored for MYCN-amplified neuroblastoma. Proc Natl Acad Sci USA. 118:e20096201182021. View Article : Google Scholar : PubMed/NCBI | |
|
Singh S, De Carlo F, Ibrahim MA, Penfornis P, Mouton AJ, Tripathi SK, Agarwal AK, Eastham L, Pasco DS, Balachandran P and Claudio PP: The oligostilbene Gnetin H is a Novel glycolysis inhibitor that regulates thioredoxin interacting protein expression and synergizes with OXPHOS inhibitor in cancer cells. Int J Mol Sci. 24:77412023. View Article : Google Scholar : PubMed/NCBI | |
|
Suski JM, Braun M, Strmiska V and Sicinski P: Targeting cell-cycle machinery in cancer. Cancer Cell. 39:759–778. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Caraci F, Chisari M, Frasca G, Chiechio S, Salomone S, Pinto A, Sortino MA and Bianchi A: Effects of phenformin on the proliferation of human tumor cell lines. Life Sci. 74:643–650. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Z, Ren L, Liu C, Xia T, Zha X and Wang S: Phenformin induces cell cycle change, apoptosis, and Mesenchymal-Epithelial transition and regulates the AMPK/mTOR/p70s6k and MAPK/ERK pathways in breast cancer cells. PLoS One. 10:e01312072015. View Article : Google Scholar : PubMed/NCBI | |
|
Viallard C and Larrivée B: Tumor angiogenesis and vascular normalization: Alternative therapeutic targets. Angiogenesis. 20:409–426. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Ramjiawan RR, Griffioen AW and Duda DG: Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy? Angiogenesis. 20:185–204. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Dodd KM, Yang J, Shen MH, Sampson JR and Tee AR: mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3. Oncogene. 34:2239–2250. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Jaidee R, Kongpetch S, Senggunprai L, Prawan A, Kukongviriyapan U and Kukongviriyapan V: Phenformin inhibits proliferation, invasion, and angiogenesis of cholangiocarcinoma cells via AMPK-mTOR and HIF-1A pathways. Naunyn Schmiedebergs Arch Pharmacol. 393:1681–1690. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Wang ZD, Wei SQ and Wang QY: Targeting oncogenic KRAS in non-small cell lung cancer cells by phenformin inhibits growth and angiogenesis. Am J Cancer Res. 5:3339–3349. 2015.PubMed/NCBI | |
|
Pastushenko I and Blanpain C: EMT transition states during tumor progression and metastasis. Trends Cell Biol. 29:212–226. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Guo Z, Zhao M, Howard EW, Zhao Q, Parris AB, Ma Z and Yang X: Phenformin inhibits growth and epithelial-mesenchymal transition of ErbB2-overexpressing breast cancer cells through targeting the IGF1R pathway. Oncotarget. 8:60342–60357. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Walsh LA and Damjanovski S: IGF-1 increases invasive potential of MCF 7 breast cancer cells and induces activation of latent TGF-β1 resulting in epithelial to mesenchymal transition. Cell Commun Signal. 9:102011. View Article : Google Scholar : PubMed/NCBI | |
|
Lin H, Li N, He H, Ying Y, Sunkara S, Luo L, Lv N, Huang D and Luo Z: AMPK Inhibits the Stimulatory Effects of TGF-β on Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition. Mol Pharmacol. 88:1062–1071. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Park JH, Kim YH, Park EH, Lee SJ, Kim H, Kim A, Lee SB, Shim S, Jang H, Myung JK, et al: Effects of metformin and phenformin on apoptosis and epithelial-mesenchymal transition in chemoresistant rectal cancer. Cancer Sci. 110:2834–2845. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Chuang CH, Dorsch M, Dujardin P, Silas S, Ueffing K, Hölken JM, Yang D, Winslow MM and Grüner BM: Altered mitochondria functionality defines a metastatic cell state in lung cancer and creates an exploitable vulnerability. Cancer Res. 81:567–579. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Pereira-Nunes A, Ferreira H, Abreu S, Guedes M, Neves NM, Baltazar F and Granja S: Combination therapy with CD147-Targeted nanoparticles carrying phenformin decreases lung cancer growth. Adv Biol (Weinh). 7:e23000802023. View Article : Google Scholar : PubMed/NCBI | |
|
Tong X, Chen Y, Zhu X, Ye Y, Xue Y, Wang R, Gao Y, Zhang W, Gao W, Xiao L, et al: Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation. EMBO Mol Med. 13:e126272021. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou Q, Kim SH, Pérez-Lorenzo R, Liu C, Huang M, Dotto GP, Zheng B and Wu X: Phenformin promotes keratinocyte differentiation via the Calcineurin/NFAT pathway. J Invest Dermatol. 141:152–163. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wu T, Zhou S, Qin M, Tang J, Yan X, Huang L, Huang M, Deng J, Xiao D, Hu X, et al: Phenformin and ataxia-telangiectasia mutated inhibitors synergistically co-suppress liver cancer cell growth by damaging mitochondria. FEBS Open Bio. 11:1440–1451. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Rajeshkumar NV, Yabuuchi S, Pai SG, De Oliveira E, Kamphorst JJ, Rabinowitz JD, Tejero H, Al-Shahrour F, Hidalgo M, Maitra A, et al: Treatment of pancreatic cancer Patient-Derived xenograft panel with metabolic inhibitors reveals efficacy of phenformin. Clin Cancer Res. 23:5639–5647. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Gunaydin B, Yigitturk G and Elbe H: Cytotoxic effects of Phenformin on ovarian cancer cells: Expression of HIF-1α and PDK1 in the hypoxic microenvironment. Rom J Morphol Embryol. 64:355–361. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Jiménez-Vacas JM, Herrero-Aguayo V, Montero-Hidalgo AJ, Sáez-Martínez P, Gómez-Gómez E, León-González AJ, Fuentes-Fayos AC, Yubero-Serrano EM, Requena-Tapia MJ, López M, et al: Clinical, cellular, and molecular evidence of the additive antitumor effects of biguanides and statins in prostate cancer. J Clin Endocrinol Metab. 106:e696–e710. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Lee B, Lee C, Moon HM, Jo SY, Jang SJ and Suh YA: Repurposing metabolic inhibitors in the treatment of colon adenocarcinoma Patient-Derived Models. Cells. 12:28592023. View Article : Google Scholar : PubMed/NCBI | |
|
Wu L, Leng D, Cun D, Foged C and Yang M: Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens. J Control Release. 260:78–91. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Thai AA, Solomon BJ, Sequist LV, Gainor JF and Heist RS: Lung cancer. Lancet. 398:535–554. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Recondo G, Facchinetti F, Olaussen KA, Besse B and Friboulet L: Making the first move in EGFR-driven or ALK-driven NSCLC: First-generation or next-generation TKI? Nat Rev Clin Oncol. 15:694–708. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Mondal A, Roberge J, Gilleran J, Peng Y, Jia D, Akel M, Patel Y, Zoltowski H, Doraiswamy A and Langenfeld J: Bone morphogenetic protein inhibitors and mitochondria targeting agents synergistically induce apoptosis-inducing factor (AIF) caspase-independent cell death in lung cancer cells. Cell Commun Signal. 20:992022. View Article : Google Scholar : PubMed/NCBI | |
|
Román M, Baraibar I, López I, Nadal E, Rolfo C, Vicent S and Gil-Bazo I: KRAS oncogene in non-small cell lung cancer: Clinical perspectives on the treatment of an old target. Mol Cancer. 17:332018. View Article : Google Scholar : PubMed/NCBI | |
|
Lee SH, Jeon Y, Kang JH, Jang H, Lee H and Kim SY: The combination of loss of ALDH1L1 function and phenformin treatment decreases tumor growth in KRAS-Driven lung cancer. Cancers (Basel). 12:13822020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang J, Nannapaneni S, Wang D, Liu F, Wang X, Jin R, Liu X, Rahman MA, Peng X, Qian G, et al: Phenformin enhances the therapeutic effect of selumetinib in KRAS-mutant non-small cell lung cancer irrespective of LKB1 status. Oncotarget. 8:59008–59022. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Dildar M, Akram S, Irfan M, Khan HU, Ramzan M, Mahmood AR, Alsaiari SA, Saeed AHM, Alraddadi MO and Mahnashi MH: Skin cancer detection: A review using deep learning techniques. Int J Environ Res Public Health. 18:54792021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang AX and Qi XY: Targeting RAS/RAF/MEK/ERK signaling in metastatic melanoma. IUBMB Life. 65:748–758. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Petti C, Vegetti C, Molla A, Bersani I, Cleris L, Mustard KJ, Formelli F, Hardie GD, Sensi M and Anichini A: AMPK activators inhibit the proliferation of human melanomas bearing the activated MAPK pathway. Melanoma Res. 22:341–350. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Trousil S, Chen S, Mu C, Shaw FM, Yao Z, Ran Y, Shakuntala T, Merghoub T, Manstein D, Rosen N, et al: Phenformin enhances the efficacy of ERK Inhibition in NF1-Mutant melanoma. J Invest Dermatol. 137:1135–1143. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Pollak M: Targeting oxidative phosphorylation: Why, when, and how. Cancer Cell. 23:263–264. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bertuccio P, Turati F, Carioli G, Rodriguez T, La Vecchia C, Malvezzi M and Negri E: Global trends and predictions in hepatocellular carcinoma mortality. J Hepatol. 67:302–309. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Veiga SR, Ge X, Mercer CA, Hernández-Álvarez MI, Thomas HE, Hernandez-Losa J, Ramón Y Cajal S, Zorzano A, Thomas G and Kozma SC: Phenformin-Induced mitochondrial dysfunction sensitizes hepatocellular carcinoma for dual inhibition of mTOR. Clin Cancer Res. 24:3767–3780. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Libson S and Lippman M: A review of clinical aspects of breast cancer. Int Rev Psychiatry. 26:4–15. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Orecchioni S, Reggiani F, Talarico G, Mancuso P, Calleri A, Gregato G, Labanca V, Noonan DM, Dallaglio K, Albini A and Bertolini F: The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells. Int J Cancer. 136:E534–E544. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Kong H, Reczek CR, McElroy GS, Steinert EM, Wang T, Sabatini DM and Chandel NS: Metabolic determinants of cellular fitness dependent on mitochondrial reactive oxygen species. Sci Adv. 6:eabb72722020. View Article : Google Scholar : PubMed/NCBI | |
|
Rosilio C, Lounnas N, Nebout M, Imbert V, Hagenbeek T, Spits H, Asnafi V, Pontier-Bres R, Reverso J, Michiels JF, et al: The metabolic perturbators metformin, phenformin and AICAR interfere with the growth and survival of murine PTEN-deficient T cell lymphomas and human T-ALL/T-LL cancer cells. Cancer Lett. 336:114–126. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Park HH, Park J, Cho HJ, Shim JK, Moon JH, Kim EH, Chang JH, Kim SY and Kang SG: Combinatorial therapeutic effect of inhibitors of aldehyde dehydrogenase and mitochondrial complex I, and the chemotherapeutic drug, temozolomide against glioblastoma tumorspheres. Molecules. 26:2822021. View Article : Google Scholar : PubMed/NCBI | |
|
Lee JS, Lee H, Woo SM, Jang H, Jeon Y, Kim HY, Song J, Lee WJ, Hong EK, Park SJ, et al: Overall survival of pancreatic ductal adenocarcinoma is doubled by Aldh7a1 deletion in the KPC mouse. Theranostics. 11:3472–3488. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Park J, Shim JK, Kang JH, Choi J, Chang JH, Kim SY and Kang SG: Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres. Neuro Oncol. 20:954–965. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Alhourani A, Førde JL, Nasrollahzadeh M, Eichacker LA, Herfindal L and Hagland HR: Graphene-based phenformin carriers for cancer cell treatment: A comparative study between oxidized and pegylated pristine graphene in human cells and zebrafish. Nanoscale Adv. 4:1668–1680. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Narise K, Okuda K, Enomoto Y, Hirayama T and Nagasawa H: Optimization of biguanide derivatives as selective antitumor agents blocking adaptive stress responses in the tumor microenvironment. Drug Des Devel Ther. 8:701–717. 2014.PubMed/NCBI | |
|
Oh-Hashi K, Irie N, Sakai T, Okuda K, Nagasawa H, Hirata Y and Kiuchi K: Elucidation of a novel phenformin derivative on glucose-deprived stress responses in HT-29 cells. Mol Cell Biochem. 419:29–40. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Oh-Hashi K, Matsumoto S, Sakai T, Nomura Y, Okuda K, Nagasawa H and Hirata Y: Elucidating the rapid action of 2-(2-chlorophenyl)ethylbiguanide on HT-29 cells under a serum- and glucose-deprived condition. Cell Biol Toxicol. 34:279–290. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Janku F, Beom SH, Moon YW, Kim TW, Shin YG, Yim DS, Kim GM, Kim HS, Kim SY, Cheong JH, et al: First-in-human study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors. Invest New Drugs. 40:1001–1010. 2022. View Article : Google Scholar : PubMed/NCBI |
