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Anticancer Original Research Papers

Combination of mTOR inhibitor PP242 and AMPK activator metformin exerts enhanced inhibitory effects on colorectal carcinoma cells in vitro by blocking multiple kinase pathways

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Pages 259-269 | Received 17 Nov 2021, Accepted 14 Jun 2022, Published online: 22 Jun 2022

References

  • Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.
  • Gulhati P, Cai Q, Li J, et al. Targeted inhibition of mammalian target of rapamycin signalling inhibits tumorigenesis of colorectal cancer. Clin Cancer Res. 2009;15(23):7207–7216.
  • Rosenwald IB, Chen JJ, Wang S, et al. Upregulation of protein synthesis initiation factor eIF-4E is an early event during Colon carcinogenesis. Oncogene. 1999;18(15):2507–2517.
  • Wang XW, Zhang YJ. Targeting mTOR network in colorectal cancer therapy. World J Gastroenterol. 2014;20(15):4178–4188.
  • Li H, Lin J, Wang X, et al. Targeting of mTORC2 prevents cell migration and promotes apoptosis in breast cancer. Breast Cancer Res Treat. 2012;134(3):1057–1066.
  • Zeng Z, Shi YX, Tsao T, et al. Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. Blood. 2012;120(13):2679–2689.
  • Blaser B, Waselle L, Dormond-Meuwly A, et al. Antitumor activities of ATP-competitive inhibitors of mTOR in Colon cancer cells. BMC Cancer. 2012;12:86.
  • Zhang Y, Zheng XF. mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors. Cell Cycle. 2012;11(3):594–603.
  • Peterson TR, Laplante M, Thoreen CC, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009;137(5):873–886.
  • Hardie DG. AMPK and raptor: matching cell growth to energy supply. Mol Cell. 2008;30(3):263–265.
  • Shaw RJ. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol (Oxf). 2009;196(1):65–80.
  • Appleyard MV, Murray KE, Coates PJ, et al. Phenformin as prophylaxis and therapy in breast cancer xenografts. Br J Cancer. 2012;106(6):1117–1122.
  • 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(22):10804–10812.
  • Chen MH, Cui SX, Cheng YN, et al. Galloyl cyclic-imide derivative CH1104I inhibits tumour invasion through suppressing matrix metalloproteinase activity. Anticancer Drug. 2008;19(10):957–965.
  • Ni D, Yi Q, Liu J, et al. A1CF-promoted colony formation and proliferation of RCC depends on DKK1-MEK/ERK signal axis. Gene. 2020;730:144299.
  • Yue B, Zhang YS, Xu HM, et al. Riccardin D-26, a synthesized macrocyclic bisbibenzyl compound, inhibits human hepatocellular carcinoma growth through induction of apoptosis in p53-dependent way. Cancer Lett. 2013;328(1):104–113.
  • Li W, Tan D, Zhang Z, et al. Activation of akt-mTOR-p70S6K pathway in angiogenesis in hepatocellular carcinoma. Oncol Rep. 2008;20(4):713–719.
  • Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12(1):9–22.
  • Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011;12(1):21–35.
  • Hara K, Maruki Y, Long X, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002;110(2):177–189.
  • Sarbassov DD, Ali SM, Kim DH, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004;14(14):1296–1302.
  • Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009;10(5):307–318.
  • García-Martínez JM, Alessi DR. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J. 2008;416(3):375–385.
  • Ikenoue T, Inoki K, Yang Q, et al. Essential function of TORC2 in PKC and akt turn motif phosphorylation, maturation and signalling. Embo J. 2008;27(14):1919–1931.
  • Zhou H, Luo Y, Huang S. Updates of mTOR inhibitors. Anticancer Agents Med Chem. 2010;10(7):571–581.
  • Luo Z, Saha AK, Xiang X, et al. AMPK, the metabolic syndrome and cancer. Trends Pharmacol Sci. 2005;26(2):69–76.
  • Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, et al. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010;9(5):1092–1099.
  • Huang X, Wullschleger S, Shpiro N, et al. Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J. 2008;412(2):211–221.
  • Martin MJ, Hayward R, Viros A, et al. Metformin accelerates the growth of BRAF V600E-driven melanoma by upregulating VEGF-A. Cancer Discov. 2012;2(4):344–355.
  • Chen G, Xu S, Renko K, et al. Metformin inhibits growth of thyroid carcinoma cells, suppresses self-renewal of derived cancer stem cells, and potentiates the effect of chemotherapeutic agents. J Clin Endocrinol Metab. 2012;97(4):E510–20.
  • Iliopoulos D, Hirsch HA, Struhl K. Metformin decreases the dose of chemotherapy for prolonging tumour remission in mouse xenografts involving multiple cancer cell types. Cancer Res. 2011;71(9):3196–3201.
  • She QB, Halilovic E, Ye Q, et al. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signalling pathways that integrates their function in tumours. Cancer Cell. 2010;18(1):39–51.
  • Dowling RJ, Topisirovic I, Alain T, et al. mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science. 2010;328(5982):1172–1176.
  • Huang H, Tindall DJ. Dynamic foxo transcription factors. J Cell Sci. 2007;120(Pt 15):2479–2487.
  • Jacinto E, Facchinetti V, Liu D, et al. Sin1/Mip1 maintains rector-mTor complex integrity and regulates akt phosphorylation and substrate specificity. Cell. 2006;127(1):125–137.
  • Frisch SM, Screaton RA. Anoikis mechanisms. Curr Opin Cell Biol. 2001;13(5):555–562.
  • Franke TF. PI3K/akt: getting it right matters. Oncogene. 2008;27(50):6473–6488.
  • Qiao M, Sheng S, Pardee AB. Metastasis and akt activation. Cell Cycle. 2008;7(19):2991–2996.
  • Soares HP, Ni Y, Kisfalvi K, et al. Different patterns of akt and ERK feedback activation in response to rapamycin, Active-Site mTOR inhibitors and metformin in pancreatic cancer cells. PLoS One. 2013;8(2):e57289.
  • Jakobsen SN, Hardie DG, Morrice N, et al. 50-AMP-activated protein kinase phosphorylates IRS-1 on ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem. 2001;276(50):46912–46916.
  • Choo AY, Yoon SO, Kim SG, et al. Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell type-specific repression of mRNA translation. Proc Natl Acad Sci U S A. 2008;105(45):17414–17419.

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