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Original Research

Paeonol Inhibits Pancreatic Cancer Cell Migration and Invasion Through the Inhibition of TGF-β1/Smad Signaling and Epithelial-Mesenchymal-Transition

, , , , , , & show all
Pages 641-651 | Published online: 29 Jan 2020

References

  • Kamisawa T, Wood LD, Itoi T, Takaori K. Pancreatic cancer. Lancet. 2016;388(10039):73–85. doi:10.1016/S0140-6736(16)00141-026830752
  • Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–620. doi:10.1016/S0140-6736(10)62307-021620466
  • Manji GA, Olive KP, Saenger YM, Oberstein P. Current and emerging therapies in metastatic pancreatic cancer. Clin Cancer Res. 2017;23(7):1670–1678. doi:10.1158/1078-0432.CCR-16-231928373365
  • Heerboth S, Housman G, Leary M, et al. EMT and tumor metastasis. Clin Transl Med. 2015;4:6. doi:10.1186/s40169-015-0048-325852822
  • Zhou P, Li B, Liu F, et al. The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer. Mol Cancer. 2017;16(1):52. doi:10.1186/s12943-017-0624-928245823
  • Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–196. doi:10.1038/nrm375824556840
  • Jolly MK, Boareto M, Huang B, et al. Implications of the hybrid epithelial/mesenchymal phenotype in metastasis. Front Oncol. 2015;5:155. doi:10.3389/fonc.2015.0015526258068
  • Lindsey S, Langhans SA. Crosstalk of oncogenic signaling pathways during epithelial-mesenchymal transition. Front Oncol. 2014;4:358. doi:10.3389/fonc.2014.0035825566498
  • Lyu ZK, Li CL, Jin Y, et al. Paeonol exerts potential activities to inhibit the growth, migration and invasion of human gastric cancer BGC823 cells via downregulating MMP2 and MMP9. Mol Med Rep. 2017;16(5):7513–7519. doi:10.3892/mmr.2017.757628944890
  • Sun Z, Du J, Hwang E, Yi TH. Paeonol extracted from paeonia suffruticosa Andr. ameliorated UVB-induced skin photoaging via DLD/Nrf2/ARE and MAPK/AP-1 pathway. Phytother Res. 2018;32(9):1741–1749. doi:10.1002/ptr.610029748977
  • Guo L, Liang J, Yang Q. Determination of paeonol in the root of cynanchum paniculatum (Bge.) Kitag. by gas chromatography. Zhongguo Zhong Yao Za Zhi. 1996;21(8):484–485, 511.9642412
  • Lei Y, Li HX, Jin WS, et al. The radiosensitizing effect of paeonol on lung adenocarcinoma by augmentation of radiation-induced apoptosis and inhibition of the PI3K/Akt pathway. Int J Radiat Biol. 2013;89(12):1079–1086. doi:10.3109/09553002.2013.82505823875954
  • Zhou HM, Sun QX, Cheng Y. Paeonol enhances the sensitivity of human ovarian cancer cells to radiotherapy-induced apoptosis due to downregulation of the phosphatidylinositol-3-kinase/Akt/phosphatase and tensin homolog pathway and inhibition of vascular endothelial growth factor. Exp Ther Med. 2017;14(4):3213–3220. doi:10.3892/etm.2017.487728912871
  • Yin J, Wu N, Zeng F, Cheng C, Kang K, Yang H. Paeonol induces apoptosis in human ovarian cancer cells. Acta Histochem. 2013;115(8):835–839. doi:10.1016/j.acthis.2013.04.00423768958
  • Fu J, Yu L, Luo J, Huo R, Zhu B. Paeonol induces the apoptosis of the SGC7901 gastric cancer cell line by downregulating ERBB2 and inhibiting the NFkappaB signaling pathway. Int J Mol Med. 2018;42(3):1473–1483. doi:10.3892/ijmm.2018.370429845222
  • Li N, Fan LL, Sun GP, et al. Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo. World J Gastroenterol. 2010;16(35):4483–4490. doi:10.3748/wjg.v16.i35.448320845518
  • Li M, Tan SY, Wang XF. Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE(2) synthesis and COX-2 expression. Oncol Rep. 2014;32(6):2845–2853. doi:10.3892/or.2014.354325322760
  • Li M, Tan SY, Zhang J, You HX. Effects of paeonol on intracellular calcium concentration and expression of RUNX3 in LoVo human colon cancer cells. Mol Med Rep. 2013;7(5):1425–1430. doi:10.3892/mmr.2013.137223504038
  • Ou Y, Li Q, Wang J, Li K, Zhou S. Antitumor and apoptosis induction effects of paeonol on mice bearing EMT6 breast carcinoma. Biomol Ther (Seoul). 2014;22(4):341–346. doi:10.4062/biomolther.2013.10625143814
  • Cai J, Chen S, Zhang W, et al. Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2. Phytomedicine. 2014;21(7):984–991. doi:10.1016/j.phymed.2014.02.01224680370
  • Saahene RO, Wang J, Wang ML, Agbo E, Pang D. The antitumor mechanism of paeonol on CXCL4/CXCR3-B signals in breast cancer through induction of tumor cell apoptosis. Cancer Biother Radiopharm. 2018;33(6):233–240. doi:10.1089/cbr.2018.245029847158
  • Zhang W, Cai J, Chen S, et al. Paclitaxel resistance in MCF-7/PTX cells is reversed by paeonol through suppression of the SET/phosphatidylinositol 3-kinase/Akt pathway. Mol Med Rep. 2015;12(1):1506–1514. doi:10.3892/mmr.2015.346825760096
  • Fan L, Song B, Sun G, Ma T, Zhong F, Wei W. Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells. PLoS One. 2013;8(5):e62627. doi:10.1371/journal.pone.006262723658755
  • Chen B, Ning M, Yang G. Effect of paeonol on antioxidant and immune regulatory activity in hepatocellular carcinoma rats. Molecules. 2012;17(4):4672–4683. doi:10.3390/molecules1704467222522397
  • Lee HJ, Kim SA, Lee HJ, et al. Paeonol oxime inhibits bFGF-induced angiogenesis and reduces VEGF levels in fibrosarcoma cells. PLoS One. 2010;5(8):e12358. doi:10.1371/journal.pone.001235820808805
  • Horng CT, Shieh PC, Tan TW, Yang WH, Tang CH. Paeonol suppresses chondrosarcoma metastasis through up-regulation of miR-141 by modulating PKCdelta and c-Src signaling pathway. Int J Mol Sci. 2014;15(7):11760–11772. doi:10.3390/ijms15071176024992595
  • Tamburrino A, Piro G, Carbone C, Tortora G, Melisi D. Mechanisms of resistance to chemotherapeutic and anti-angiogenic drugs as novel targets for pancreatic cancer therapy. Front Pharmacol. 2013;4:56. doi:10.3389/fphar.2013.0005623641216
  • Hidalgo M, Alvarez R, Gallego J, et al. Consensus guidelines for diagnosis, treatment and follow-up of patients with pancreatic cancer in Spain. Clin Transl Oncol. 2017;19(6):667–681. doi:10.1007/s12094-016-1594-x27995549
  • Peixoto RD, Speers C, McGahan CE, Renouf DJ, Schaeffer DF, Kennecke HF. Prognostic factors and sites of metastasis in unresectable locally advanced pancreatic cancer. Cancer Med. 2015;4(8):1171–1177. doi:10.1002/cam4.45925891650
  • Barrallo-Gimeno A, Nieto MA. The snail genes as inducers of cell movement and survival: implications in development and cancer. Development. 2005;132(14):3151–3161. doi:10.1242/dev.0190715983400
  • Aigner K, Dampier B, Descovich L, et al. The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Oncogene. 2007;26(49):6979–6988. doi:10.1038/sj.onc.121050817486063
  • Gaianigo N, Melisi D, Carbone C. EMT and treatment resistance in pancreatic cancer. Cancers (Basel). 2017;9(9):122. doi:10.3390/cancers9090122
  • Nakajima S, Doi R, Toyoda E, et al. N-cadherin expression and epithelial-mesenchymal transition in pancreatic carcinoma. Clin Cancer Res. 2004;10(12 Pt 1):4125–4133. doi:10.1158/1078-0432.CCR-0578-0315217949
  • Mrozik KM, Blaschuk OW, Cheong CM, Zannettino ACW, Vandyke K. N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer. 2018;18(1):939. doi:10.1186/s12885-018-4845-030285678
  • Wang S, Huang S, Sun YL. Epithelial-mesenchymal transition in pancreatic cancer: a review. Biomed Res Int. 2017;2017:2646148. doi:10.1155/2017/264614829379795
  • David CJ, Huang YH, Chen M, et al. TGF-beta tumor suppression through a lethal EMT. Cell. 2016;164(5):1015–1030. doi:10.1016/j.cell.2016.01.00926898331
  • O’Connor JW, Gomez EW. Biomechanics of TGFbeta-induced epithelial-mesenchymal transition: implications for fibrosis and cancer. Clin Transl Med. 2014;3:23. doi:10.1186/2001-1326-3-2325097726
  • Moustakas A, Heldin CH. Mechanisms of TGFbeta-induced epithelial-mesenchymal transition. J Clin Med. 2016;5:7. doi:10.3390/jcm5070063
  • Xu W, Yang Z, Lu N. A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adh Migr. 2015;9(4):317–324. doi:10.1080/19336918.2015.101668626241004
  • Haque S, Morris JC. Transforming growth factor-beta: a therapeutic target for cancer. Hum Vaccin Immunother. 2017;13(8):1741–1750. doi:10.1080/21645515.2017.132710728575585
  • Zhang L, Tao L, Shi T, et al. Paeonol inhibits B16F10 melanoma metastasis in vitro and in vivo via disrupting proinflammatory cytokines-mediated NF-kappaB and STAT3 pathways. IUBMB Life. 2015;67(10):778–788. doi:10.1002/iub.143526452780
  • Sun GP, Wang H, Xu SP, et al. Anti-tumor effects of paeonol in a HepA-hepatoma bearing mouse model via induction of tumor cell apoptosis and stimulation of IL-2 and TNF-alpha production. Eur J Pharmacol. 2008;584(2–3):246–252. doi:10.1016/j.ejphar.2008.02.01618329639
  • Ellenrieder V, Hendler SF, Boeck W, et al. Transforming growth factor beta1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res. 2001;61(10):4222–4228.11358848
  • Wang H, Wu J, Zhang Y, et al. Transforming growth factor beta-induced epithelial-mesenchymal transition increases cancer stem-like cells in the PANC-1 cell line. Oncol Lett. 2012;3(1):229–233. doi:10.3892/ol.2011.44822740886
  • Lebrun JJ. The dual role of TGFbeta in human cancer: from tumor suppression to cancer metastasis. ISRN Mol Biol. 2012;2012:381428.27340590
  • Kashima R, Hata A. The role of TGF-beta superfamily signaling in neurological disorders. Acta Biochim Biophys Sin (Shanghai). 2018;50(1):106–120. doi:10.1093/abbs/gmx12429190314
  • Pardali E, Ten Dijke P. TGFbeta signaling and cardiovascular diseases. Int J Biol Sci. 2012;8(2):195–213. doi:10.7150/ijbs.8.19522253564
  • Jakowlew SB. Transforming growth factor-beta in cancer and metastasis. Cancer Metastasis Rev. 2006;25(3):435–457. doi:10.1007/s10555-006-9006-216951986
  • Nie D, Sun H, Shi Z, Zhou X. The effects of combination of paeonol and PNS on TGF-β/smad pathway in ventricular remodeling after myocardial infarction in rats. Tianjin Med J. 2016;44(4):449–452.
  • Wu S, Liu L, Yang S, et al. Paeonol alleviates CCl4-induced liver fibrosis through suppression of hepatic stellate cells activation via inhibiting the TGF-beta/smad3 signaling. Immunopharmacol Immunotoxicol. 2019;41(3):438–445. doi:10.1080/08923973.2019.161342731119954