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Review

Silibinin: a potential old drug for cancer therapy

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Pages 1323-1330 | Received 16 Apr 2016, Accepted 29 Jun 2016, Published online: 18 Jul 2016

References

  • Gharagozloo M, Khoshdel Z, Amirghofran Z. The effect of an iron (III) chelator, silybin, on the proliferation and cell cycle of Jurkat cells: a comparison with desferrioxamine. Eur J Pharmacol. 2008;589(1–3):1–7.
  • Gharagozloo M, Moayedi B, Zakerinia M, et al. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. Fundam Clin Pharmacol. 2009;23(3):359–365.
  • Travis WD. Classification of lung cancer. Semin Roentgenol. 2011;46(3):178–186.
  • Van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011;378(9804):1741–1755.
  • Sadava D, Kane SE. Silibinin reverses drug resistance in human small-cell lung carcinoma cells. Cancer Lett. 2013;339(1):102–106.
  • Bunn PA Jr., Minna J, Augustyn A, et al. Small cell lung cancer: can recent advances in biology and molecular biology be translated into improved outcomes? J Thorac Oncol. 2016;11(4):453–474.
  • Nishio K, Nakamura T, Koh Y, et al. Drug resistance in lung cancer. Curr Opin Oncol. 1999;11(2):109–115.
  • Milic N, Milosevic N, Suvajdzic L, et al. New therapeutic potentials of milk thistle (Silybum marianum). Nat Prod Commun. 2013;8(12):1801–1810.
  • Zholobenko A, Modriansky M. Silymarin and its constituents in cardiac preconditioning. Fitoterapia. 2014;97:122–132.
  • Vargas-Mendoza N, Madrigal-Santillan E, Morales-Gonzalez A, et al. Hepatoprotective effect of silymarin. World J Hepatol. 2014;6(3):144–149.
  • Madrigal-Santillan E, Madrigal-Bujaidar E, Alvarez-Gonzalez I, et al. Review of natural products with hepatoprotective effects. World J Gastroenterol. 2014;20(40):14787–14804.
  • Mateen S, Raina K, Agarwal R. Chemopreventive and anti-cancer efficacy of silibinin against growth and progression of lung cancer. Nutr Cancer. 2013;65(Suppl 1):3–11.
  • Sharma G, Singh RP, Chan DC, et al. Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells. Anticancer Res. 2003;23(3B):2649–2655.
  • Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
  • Mateen S, Tyagi A, Agarwal C, et al. Silibinin inhibits human nonsmall cell lung cancer cell growth through cell-cycle arrest by modulating expression and function of key cell-cycle regulators. Mol Carcinog. 2010;49(3):247–258.
  • Yu H, Jove R. The STATs of cancer–new molecular targets come of age. Nat Rev Cancer. 2004;4(2):97–105.
  • Haura EB, Zheng Z, Song L, et al. Activated epidermal growth factor receptor-Stat-3 signaling promotes tumor survival in vivo in non-small cell lung cancer. Clin Cancer Res. 2005;11(23):8288–8294.
  • Xu YH, Lu S. A meta-analysis of STAT3 and phospho-STAT3 expression and survival of patients with non-small-cell lung cancer. Eur J Surg Oncol. 2014;40(3):311–317.
  • Chittezhath M, Deep G, Singh RP, et al. Silibinin inhibits cytokine-induced signaling cascades and down-regulates inducible nitric oxide synthase in human lung carcinoma A549 cells. Mol Cancer Ther. 2008;7(7):1817–1826.
  • Liang Z, Yang Y, Wang H, et al. Inhibition of SIRT1 signaling sensitizes the antitumor activity of silybin against human lung adenocarcinoma cells in vitro and in vivo. Mol Cancer Ther. 2014;13(7):1860–1872.
  • Kavitha CV, Deep G, Gangar SC, et al. Silibinin inhibits prostate cancer cells- and RANKL-induced osteoclastogenesis by targeting NFATc1, NF-kappaB, and AP-1 activation in RAW264.7 cells. Mol Carcinog. 2014;53(3):169–180.
  • Attard G, Parker C, Eeles RA, et al. Prostate cancer. Lancet. 2016;387(10013):70–82.
  • Wu KJ, Zeng J, Zhu GD, et al. Silibinin inhibits prostate cancer invasion, motility and migration by suppressing vimentin and MMP-2 expression. Acta Pharmacol Sin. 2009;30(8):1162–1168.
  • Tyagi A, Sharma Y, Agarwal C, et al. Silibinin impairs constitutively active TGFalpha-EGFR autocrine loop in advanced human prostate carcinoma cells. Pharm Res. 2008;25(9):2143–2150.
  • Singh RP, Raina K, Deep G, et al. Silibinin suppresses growth of human prostate carcinoma PC-3 orthotopic xenograft via activation of extracellular signal-regulated kinase 1/2 and inhibition of signal transducers and activators of transcription signaling. Clin Cancer Res. 2009;15(2):613–621. .
  • Lu W, Lin C, King TD, et al. Silibinin inhibits Wnt/beta-catenin signaling by suppressing Wnt co-receptor LRP6 expression in human prostate and breast cancer cells. Cell Signal. 2012;24(12):2291–2296.
  • Kim SH, Kim KY, Yu SN, et al. Autophagy inhibition enhances silibinin-induced apoptosis by regulating reactive oxygen species production in human prostate cancer PC-3 cells. Biochem Biophys Res Commun. 2015;468(1–2):151–156.
  • Prajapati V, Kale RK, Singh RP. Silibinin combination with arsenic strongly inhibits survival and invasiveness of human prostate carcinoma cells. Nutr Cancer. 2015;67(4):647–658.
  • Nambiar DK, Deep G, Singh RP, et al. Silibinin inhibits aberrant lipid metabolism, proliferation and emergence of androgen-independence in prostate cancer cells via primarily targeting the sterol response element binding protein 1. Oncotarget. 2014;5(20):10017–10033.
  • Ci X, Xing C, Zhang B, et al. KLF5 inhibits angiogenesis in PTEN-deficient prostate cancer by attenuating AKT activation and subsequent HIF1alpha accumulation. Mol Cancer. 2015;14:91.
  • Borre M, Nerstrom B, Overgaard J. Association between immunohistochemical expression of vascular endothelial growth factor (VEGF), VEGF-expressing neuroendocrine-differentiated tumor cells, and outcome in prostate cancer patients subjected to watchful waiting. Clin Cancer Res. 2000;6(5):1882–1890.
  • Jung HJ, Park JW, Lee JS, et al. Silibinin inhibits expression of HIF-1alpha through suppression of protein translation in prostate cancer cells. Biochem Biophys Res Commun. 2009;390(1):71–76.
  • Zadra G, Photopoulos C, Loda M. The fat side of prostate cancer. Biochim Biophys Acta. 2013;1831(10):1518–1532.
  • Huang WC, Li X, Liu J, et al. Activation of androgen receptor, lipogenesis, and oxidative stress converged by SREBP-1 is responsible for regulating growth and progression of prostate cancer cells. Mol Cancer Res. 2012;10(1):133–142.
  • Chung DC. The genetic basis of colorectal cancer: insights into critical pathways of tumorigenesis. Gastroenterology. 2000;119(3):854–865.
  • Agarwal C, Singh RP, Dhanalakshmi S, et al. Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells. Oncogene. 2003;22(51):8271–8282.
  • Velmurugan B, Gangar SC, Kaur M, et al. Silibinin exerts sustained growth suppressive effect against human colon carcinoma SW480 xenograft by targeting multiple signaling molecules. Pharm Res. 2010;27(10):2085–2097.
  • Woo SM, Min KJ, Kim S, et al. Silibinin induces apoptosis of HT29 colon carcinoma cells through early growth response-1 (EGR-1)-mediated non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) up-regulation. Chem Biol Interact. 2014;211:36–43.
  • Shi MD, Lin HH, Lee YC, et al. Inhibition of cell-cycle progression in human colorectal carcinoma Lovo cells by andrographolide. Chem Biol Interact. 2008;174(3):201–210.
  • Karim BO, Rhee KJ, Liu G, et al. Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc(-/+) mice. BMC Cancer. 2013;13:157.
  • Sangeetha N, Nalini N. Silibinin modulates caudal-type homeobox transcription factor (CDX2), an intestine specific tumor suppressor to abrogate colon cancer in experimental rats. Hum Exp Toxicol. 2015;34(1):56–64.
  • Kauntz H, Bousserouel S, Gosse F, et al. Silibinin triggers apoptotic signaling pathways and autophagic survival response in human colon adenocarcinoma cells and their derived metastatic cells. Apoptosis. 2011;16(10):1042–1053.
  • Pirouzpanah MB, Sabzichi M, Pirouzpanah S, et al. Silibilin-induces apoptosis in breast cancer cells by modulating p53, p21, Bak and Bcl-XL pathways. Asian Pac J Cancer Prev. 2015;16(5):2087–2092.
  • Jiang K, Wang W, Jin X, et al. Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells. Oncol Rep. 2015;33(6):2711–2718.
  • Yousefi M, Ghaffari SH, Zekri A, et al. Silibinin induces apoptosis and inhibits proliferation of estrogen receptor (ER)-negative breast carcinoma cells through suppression of nuclear factor kappa B activation. Arch Iran Med. 2014;17(5):366–371.
  • Kim TH, Woo JS, Kim YK, et al. Silibinin induces cell death through reactive oxygen species-dependent downregulation of notch-1/ERK/Akt signaling in human breast cancer cells. J Pharmacol Exp Ther. 2014;349(2):268–278.
  • Zheng N, Zhang P, Huang H, et al. ERalpha down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells. J Pharmacol Sci. 2015;128(3):97–107.
  • Zheng N, Liu L, Liu W, et al. ERbeta up-regulation was involved in silibinin-induced growth inhibition of human breast cancer MCF-7 cells. Arch Biochem Biophys. 2016;591:141–149.
  • Oh SJ, Jung SP, Han J, et al. Silibinin inhibits TPA-induced cell migration and MMP-9 expression in thyroid and breast cancer cells. Oncol Rep. 2013;29(4):1343–1348.
  • Kim S, Jeon M, Lee J, et al. Induction of fibronectin in response to epidermal growth factor is suppressed by silibinin through the inhibition of STAT3 in triple negative breast cancer cells. Oncol Rep. 2014;32(5):2230–2236.
  • Bosch-Barrera J, Menendez JA. Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy. Cancer Treat Rev. 2015;41(6):540–546.
  • Zadeh MM, Ranji N, Motamed N. Deregulation of miR-21 and miR-155 and their putative targets after silibinin treatment in T47D breast cancer cells. Iran J Basic Med Sci. 2015;18(12):1209–1214.
  • Zadeh MM, Motamed N, Ranji N, et al. Silibinin-induced apoptosis and downregulation of MicroRNA-21 and MicroRNA-155 in MCF-7 human breast cancer cells. J Breast Cancer. 2016;19(1):45–52.
  • Mahmoodi N, Motamed N, Paylakhi SH, et al. Comparing the effect of silybin and silybin advanced on viability and HER2 expression on the human breast cancer SKBR3 cell line by no serum starvation. Iran J Pharm Res. 2015;14(2):521–530.
  • Tyagi AK, Agarwal C, Singh RP, et al. Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells. Biochem Biophys Res Commun. 2003;312(4):1178–1184.
  • Tyagi A, Singh RP, Agarwal C, et al. Silibinin activates p53-caspase 2 pathway and causes caspase-mediated cleavage of Cip1/p21 in apoptosis induction in bladder transitional-cell papilloma RT4 cells: evidence for a regulatory loop between p53 and caspase 2. Carcinogenesis. 2006;27(11):2269–2280.
  • Tyagi A, Raina K, Singh RP, et al. Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in male ICR mice. Mol Cancer Ther. 2007;6(12 Pt 1):3248–3255.
  • Singh RP, Tyagi A, Sharma G, et al. Oral silibinin inhibits in vivo human bladder tumor xenograft growth involving down-regulation of survivin. Clin Cancer Res. 2008;14(1):300–308.
  • Zeng J, Sun Y, Wu K, et al. Chemopreventive and chemotherapeutic effects of intravesical silibinin against bladder cancer by acting on mitochondria. Mol Cancer Ther. 2011;10(1):104–116.
  • Wu K, Ning Z, Zeng J, et al. Silibinin inhibits beta-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness. Cell Signal. 2013;25(12):2625–2633.
  • Bosch-Barrera J, Corominas-Faja B, Cuyas E, et al. Silibinin administration improves hepatic failure due to extensive liver infiltration in a breast cancer patient. Anticancer Res. 2014;34(8):4323–4327.
  • Gu HR, Park SC, Choi SJ, et al. Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells. Clin Mol Hepatol. 2015;21(1):49–59.
  • Lah JJ, Cui W, Hu KQ. Effects and mechanisms of silibinin on human hepatoma cell lines. World J Gastroenterol. 2007;13(40):5299–5305.
  • Ghasemi R, Ghaffari SH, Momeny M, et al. Multitargeting and antimetastatic potentials of silibinin in human HepG-2 and PLC/PRF/5 hepatoma cells. Nutr Cancer. 2013;65(4):590–599.
  • Momeny M, Khorramizadeh MR, Ghaffari SH, et al. Effects of silibinin on cell growth and invasive properties of a human hepatocellular carcinoma cell line, HepG-2, through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation. Eur J Pharmacol. 2008;591(1–3):13–20.
  • Cui W, Gu F, Hu KQ. Effects and mechanisms of silibinin on human hepatocellular carcinoma xenografts in nude mice. World J Gastroenterol. 2009;15(16):1943–1950.
  • Garcia-Maceira P, Mateo J. Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signalling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene. 2009;28(3):313–324.
  • Brandon-Warner E, Sugg JA, Schrum LW, et al. Silibinin inhibits ethanol metabolism and ethanol-dependent cell proliferation in an in vitro model of hepatocellular carcinoma. Cancer Lett. 2010;291(1):120–129.
  • Bousserouel S, Bour G, Kauntz H, et al. Silibinin inhibits tumor growth in a murine orthotopic hepatocarcinoma model and activates the TRAIL apoptotic signaling pathway. Anticancer Res. 2012;32(7):2455–2462.
  • Zhang S, Yang Y, Liang Z, et al. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells. PLoS One. 2013;8(12):e83699.
  • Bosch-Barrera J, Sais E, Canete N, et al. Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin. Oncotarget. 2016 Mar 3.

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