Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Targeting the HIF-1α/Cav-1 Pathway with a Chicory Extract/Daidzein Combination Plays a Potential Role in Retarding Hepatocellular Carcinoma

Author(s): Sherin Zakaria, Reem Nawaya, Nabil M. Abdel-Hamid, Ramadan A. Eldomany and Mamdouh M. El-Shishtawy*

Volume 21, Issue 10, 2021

Published on: 11 August, 2021

Page: [881 - 896] Pages: 16

DOI: 10.2174/1568009621666210811121120

Price: $65

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most rapidly growing solid cancers, that is characterized by hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates tumor proliferation and metastasis. It induces caveolin-1 (Cav-1) expression, a glycoprotein found on the membrane surface, then Cav-1 triggers angiogenesis and metastasis in HCC.

Objective: We hypothesize that targeting HIF-1α and consequently, Cav-1 using the antioxidant natural compound such as chicoric acid and a Cav-1 inhibitor daidzein (DAZ) could be a useful approach in the management of HCC. This study was conducted to investigate the possible therapeutic efficacy of standardized chicory leaf extract (SCLE) and DAZ via modulation of HIF-1α and Cav-1 in HCC rats.

Methods: Diethyl nitrosamine (DENA) was used for HCC induction. After the induction period, four groups (10 rats for each) were treated with SCLE, DAZ, a combination of both, as well as sorafenib, all compared to the non-treated control. We assessed hepatic HIF-1α protein expression, Cav-1 gene expression, serum level of AFP, hepatic tissue content of VEGF, MMP-9, oxidative stress markers MDA and SOD.

Results: DAZ, SCLE, and their combination, significantly down-regulated the expression of HIF-1α, Cav-1, and consequently dampened MMP-9, VEGF, hepatic content. It has been observed that the combination treatment showed a synergistic effect compared to either treatment alone. Importantly, the combination treatment exhibited a significantly more potent effect than sorafenib.

Conclusion: This study showed the potential role of the HIF-1α/Cav-1 pathway in HCC progression, moreover, SCLE and DAZ showed a potent efficacy in retarding HCC via modulation of this pathway.

Keywords: Hepatocellular carcinoma, diethyl nitrosamine, chicory leaf extract, daidzein, hypoxia-inducible factor-1α, caveolin- 1.

« Previous
Graphical Abstract

[1]
Mo’men, Y.S.; Hussein, R.M.; Kandeil, M.A. A novel chemoprotective effect of tiopronin against diethylnitrosamine-induced hepatocellular carcinoma in rats: Role of ASK1/P38 MAPK-P53 signalling cascade. Clin. Exp. Pharmacol. Physiol., 2020, 47(2), 322-332.
[http://dx.doi.org/10.1111/1440-1681.13204] [PMID: 31663622]
[2]
Ziada, D.H.; El Sadany, S.; Soliman, H.; Abd-Elsalam, S.; Salama, M.; Hawash, N.; Selim, A.; Hamisa, M.; Elsabagh, H.M. Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study. J. Egypt. Natl. Canc. Inst., 2016, 28(4), 257-262.
[http://dx.doi.org/10.1016/j.jnci.2016.06.001] [PMID: 27378258]
[3]
Marrero, J.A.; Kulik, L.M.; Sirlin, C.B.; Zhu, A.X.; Finn, R.S.; Abecassis, M.M.; Roberts, L.R.; Heimbach, J.K. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology, 2018, 68(2), 723-750.
[http://dx.doi.org/10.1002/hep.29913] [PMID: 29624699]
[4]
Huang, C.S.; Lyu, S.C.; Hu, M.L. Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells. Invest. New Drugs, 2012, 30(4), 1449-1459.
[http://dx.doi.org/10.1007/s10637-011-9727-0] [PMID: 21826440]
[5]
Llovet, J.M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, J.F.; de Oliveira, A.C.; Santoro, A.; Raoul, J.L.; Forner, A.; Schwartz, M.; Porta, C.; Zeuzem, S.; Bolondi, L.; Greten, T.F.; Galle, P.R.; Seitz, J.F.; Borbath, I.; Häussinger, D.; Giannaris, T.; Shan, M.; Moscovici, M.; Voliotis, D.; Bruix, J. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med., 2008, 359(4), 378-390.
[http://dx.doi.org/10.1056/NEJMoa0708857] [PMID: 18650514]
[6]
Chen, K.F.; Yu, H.C.; Liu, T.H.; Lee, S.S.; Chen, P.J.; Cheng, A.L. Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation. J. Hepatol., 2010, 52(1), 88-95.
[http://dx.doi.org/10.1016/j.jhep.2009.10.011] [PMID: 19913321]
[7]
Aglan, H.A.; Ahmed, H.H.; El-Toumy, S.A.; Mahmoud, N.S. Gallic acid against hepatocellular carcinoma: An integrated scheme of the potential mechanisms of action from in vivo study. Tumour Biol., 2017, 39(6), 1010428317699127.
[http://dx.doi.org/10.1177/1010428317699127] [PMID: 28618930]
[8]
McKeown, S.R. Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. Br. J. Radiol., 2014, 87(1035), 20130676.
[http://dx.doi.org/10.1259/bjr.20130676] [PMID: 24588669]
[9]
Denko, N.C.; Fontana, L.A.; Hudson, K.M.; Sutphin, P.D.; Raychaudhuri, S.; Altman, R.; Giaccia, A.J. Investigating hypoxic tumor physiology through gene expression patterns. Oncogene, 2003, 22(37), 5907-5914.
[http://dx.doi.org/10.1038/sj.onc.1206703] [PMID: 12947397]
[10]
Brahimi-Horn, M.C.; Chiche, J.; Pouysségur, J. Hypoxia and cancer. J. Mol. Med. (Berl.), 2007, 85(12), 1301-1307.
[http://dx.doi.org/10.1007/s00109-007-0281-3] [PMID: 18026916]
[11]
Chang, Q.; Jurisica, I.; Do, T.; Hedley, D.W. Hypoxia predicts aggressive growth and spontaneous metastasis formation from orthotopically grown primary xenografts of human pancreatic cancer. Cancer Res., 2011, 71(8), 3110-3120.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4049] [PMID: 21343390]
[12]
Arslan, A.; Demir, H.; Ozbay, M.F.; Arslan, H. Evaluation of lipid peroxidation and some antioxidant activities in patients with primary and metastatic liver cancer. J. Cancer Ther., 2014.
[http://dx.doi.org/10.4236/jct.2014.52024]
[13]
Lluis, J.M.; Buricchi, F.; Chiarugi, P.; Morales, A.; Fernandez-Checa, J.C. Dual role of mitochondrial reactive oxygen species in hypoxia signaling: Activation of nuclear factor-kappaB via c-SRC and oxidant-dependent cell death. Cancer Res., 2007, 67(15), 7368-7377.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0515] [PMID: 17671207]
[14]
Hielscher, A.; Gerecht, S. Hypoxia and free radicals: Role in tumor progression and the use of engineering-based platforms to address these relationships. Free Radic. Biol. Med., 2015, 79, 281-291.
[http://dx.doi.org/10.1016/j.freeradbiomed.2014.09.015] [PMID: 25257256]
[15]
Mao, X.; Wong, S.Y.; Tse, E.Y.; Ko, F.C.; Tey, S.K.; Yeung, Y.S.; Man, K.; Lo, R.C.; Ng, I.O.; Yam, J.W. Mechanisms through which hypoxia-induced caveolin-1 drives tumorigenesis and metastasis in hepatocellular carcinoma. Cancer Res., 2016, 76(24), 7242-7253.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1031] [PMID: 27784747]
[16]
Du, C.; Chen, L.; Zhang, H.; Wang, Z.; Liu, W.; Xie, X.; Xie, M. Caveolin-1 limits the contribution of BKCa channel to MCF-7 breast cancer cell proliferation and invasion. Int. J. Mol. Sci., 2014, 15(11), 20706-20722.
[http://dx.doi.org/10.3390/ijms151120706] [PMID: 25397596]
[17]
Tang, Y.; Zeng, X.; He, F.; Liao, Y.; Qian, N.; Toi, M. Caveolin-1 is related to invasion, survival, and poor prognosis in hepatocellular cancer. Med. Oncol., 2012, 29(2), 977-984.
[http://dx.doi.org/10.1007/s12032-011-9900-5] [PMID: 21416157]
[18]
Wang, X.; Wu, J.; Chiba, H.; Umegaki, K.; Yamada, K.; Ishimi, Y. Puerariae radix prevents bone loss in ovariectomized mice. J. Bone Miner. Metab., 2003, 21(5), 268-275.
[http://dx.doi.org/10.1007/s00774-003-0420-z] [PMID: 12928827]
[19]
Xu, L.; Qu, X.; Li, H.; Li, C.; Liu, J.; Zheng, H.; Liu, Y. Src/caveolin-1-regulated EGFR activation antagonizes TRAIL-induced apoptosis in gastric cancer cells. Oncol. Rep., 2014, 32(1), 318-324.
[http://dx.doi.org/10.3892/or.2014.3183] [PMID: 24840271]
[20]
Shi, Y.; Tan, S.H.; Ng, S.; Zhou, J.; Yang, N.D.; Koo, G.B.; McMahon, K.A.; Parton, R.G.; Hill, M.M.; Del Pozo, M.A.; Kim, Y.S.; Shen, H.M. Critical role of CAV1/caveolin-1 in cell stress responses in human breast cancer cells via modulation of lysosomal function and autophagy. Autophagy, 2015, 11(5), 769-784.
[http://dx.doi.org/10.1080/15548627.2015.1034411] [PMID: 25945613]
[21]
Yang, H.; Guan, L.; Li, S.; Jiang, Y.; Xiong, N.; Li, L.; Wu, C.; Zeng, H.; Liu, Y. Mechanosensitive caveolin-1 activation-induced PI3K/Akt/mTOR signaling pathway promotes breast cancer motility, invadopodia formation and metastasis in vivo. Oncotarget, 2016, 7(13), 16227-16247.
[http://dx.doi.org/10.18632/oncotarget.7583] [PMID: 26919102]
[22]
Xie, Z.; Zeng, X.; Waldman, T.; Glazer, R.I. Transformation of mammary epithelial cells by 3-phosphoinositide- dependent protein kinase-1 activates beta-catenin and c-Myc, and down-regulates caveolin-1. Cancer Res., 2003, 63(17), 5370-5375.
[PMID: 14500370]
[23]
Zou, W.; Ma, X.; Hua, W.; Chen, B.; Cai, G. Caveolin-1 mediates chemoresistance in cisplatin-resistant ovarian cancer cells by targeting apoptosis through the Notch-1/Akt/NF-κB pathway. Oncol. Rep., 2015, 34(6), 3256-3263.
[http://dx.doi.org/10.3892/or.2015.4320] [PMID: 26503358]
[24]
Gao, P.; Zhang, H.; Dinavahi, R.; Li, F.; Xiang, Y.; Raman, V.; Bhujwalla, Z.M.; Felsher, D.W.; Cheng, L.; Pevsner, J.; Lee, L.A.; Semenza, G.L.; Dang, C.V. HIF-dependent antitumorigenic effect of antioxidants in vivo. Cancer Cell, 2007, 12(3), 230-238.
[http://dx.doi.org/10.1016/j.ccr.2007.08.004] [PMID: 17785204]
[25]
Upadhyay, J.; Kesharwani, R.K.; Misra, K. Comparative study of antioxidants as cancer preventives through inhibition of HIF-1 alpha activity. Bioinformation, 2009, 4(6), 233-236.
[http://dx.doi.org/10.6026/97320630004233] [PMID: 20975915]
[26]
Al-Snafi, A.E. Medical importance of Cichorium intybus–A review. IOSR J. Pharm, 2016, 6, 41-56.
[27]
Hassan, H.A.; Serag, H.M.; Abdel-Hamid, N.M.; Amr, M.M. Synergistically curative effect of chicory extract and cisplatin against thioacetamide-induced hepatocellular carcinoma. Hepatoma Res., 2015, 1, 147-154.
[http://dx.doi.org/10.4103/2394-5079.167376]
[28]
Sultana, S.; Perwaiz, S.; Iqbal, M.; Athar, M. Crude extracts of hepatoprotective plants, Solanum nigrum and Cichorium intybus inhibit free radical-mediated DNA damage. J. Ethnopharmacol., 1995, 45(3), 189-192.
[http://dx.doi.org/10.1016/0378-8741(94)01214-K] [PMID: 7623482]
[29]
Abu-Dahab, R.; Afifi, F. Antiproliferative activity of selected medicinal plants of Jordan against a breast adenocarcinoma cell line (MCF7). Sci. Pharm., 2007, 75, 121-146.
[http://dx.doi.org/10.3797/scipharm.2007.75.121]
[30]
Saleem, M.; Abbas, K.; Naseer, F.; Ahmad, M.; Javed, F.; Hussain, K.; Asima, S. Anticancer activity of n-hexane extract of Cichorium intybus on lymphoblastic leukemia cells (Jurkat cells). Afr. J. Plant Sci., 2014, 8, 315-319.
[http://dx.doi.org/10.5897/AJPS2013.1021]
[31]
Mushtaq, A.; Ahmad, M.; Jabeen, Q. Pharmacological role of Cichorium intybus as a hepatoprotective agent on the elevated serum marker enzymes level in albino rats intoxicated with nimesulide. Int. J. Curr. Pharm. Res., 2013, 5, 25-30.
[32]
Sloley, B.D.; Urichuk, L.J.; Tywin, C.; Coutts, R.T.; Pang, P.K.; Shan, J.J. Comparison of chemical components and antioxidants capacity of different Echinacea species. J. Pharm. Pharmacol., 2001, 53(6), 849-857.
[http://dx.doi.org/10.1211/0022357011776009] [PMID: 11428661]
[33]
Zhang, H.L.; Dai, L.H.; Wu, Y.H.; Yu, X.P.; Zhang, Y.Y.; Guan, R.F.; Liu, T.; Zhao, J. Evaluation of hepatocyteprotective and anti-hepatitis B virus properties of Cichoric acid from Cichorium intybus leaves in cell culture. Biol. Pharm. Bull., 2014, 37(7), 1214-1220.
[http://dx.doi.org/10.1248/bpb.b14-00137] [PMID: 24759764]
[34]
Tsai, Y.L.; Chiu, C.C.; Yi-Fu Chen, J.; Chan, K.C.; Lin, S.D. Cytotoxic effects of Echinacea purpurea flower extracts and cichoric acid on human colon cancer cells through induction of apoptosis. J. Ethnopharmacol., 2012, 143(3), 914-919.
[http://dx.doi.org/10.1016/j.jep.2012.08.032] [PMID: 22971663]
[35]
Masilamani, M.; Wei, J.; Sampson, H.A. Regulation of the immune response by soybean isoflavones. Immunol. Res., 2012, 54(1-3), 95-110.
[http://dx.doi.org/10.1007/s12026-012-8331-5] [PMID: 22484990]
[36]
Sun, M-Y.; Ye, Y.; Xiao, L.; Rahman, K.; Xia, W.; Zhang, H. Daidzein: A review of pharmacological effects. Afr. J. Tradit. Complement. Altern. Med., 2016, 13, 117-132.
[http://dx.doi.org/10.4314/ajtcam.v13i3.15]
[37]
Park, H.J.; Jeon, Y.K.; You, D.H.; Nam, M.J. Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells. Food Chem. Toxicol., 2013, 60, 542-549.
[http://dx.doi.org/10.1016/j.fct.2013.08.022] [PMID: 23959101]
[38]
McFarland, M. Method development and validation for determination of chicoric acid in aqueous ethanol extract of Cichorium intybus L. using reverse phase liquid chromatography.Northeastern Illinois University, 2016.
[39]
Babu, L.H.; Perumal, S.; Balasubramanian, M.P. Myrtenal, a natural monoterpene, down-regulates TNF-α expression and suppresses carcinogen-induced hepatocellular carcinoma in rats. Mol. Cell. Biochem., 2012, 369(1-2), 183-193.
[http://dx.doi.org/10.1007/s11010-012-1381-0] [PMID: 22763672]
[40]
Nallamilli, B.R.; Kumar, C.S.P.; Reddy, K.V.; Prasanna, M.L.; Maruthi, V.; Sucharita, P. Hepatoprotective activity of Cichorium intybus (Linn.) root extract against carbon tetrachloride induced hepatotoxicity in albino Wistar rats. Drug Inven. Today, 2013, 5, 311-314.
[http://dx.doi.org/10.1016/j.dit.2013.08.005]
[41]
He, Y.; Wu, X.; Cao, Y.; Hou, Y.; Chen, H.; Wu, L.; Lu, L.; Zhu, W.; Gu, Y. Daidzein exerts anti-tumor activity against bladder cancer cells via inhibition of FGFR3 pathway. Neoplasma, 2016, 63(4), 523-531.
[http://dx.doi.org/10.4149/neo_2016_405] [PMID: 27268915]
[42]
Alsaied, O.A.; Sangwan, V.; Banerjee, S.; Krosch, T.C.; Chugh, R.; Saluja, A.; Vickers, S.M.; Jensen, E.H. Sorafenib and triptolide as combination therapy for hepatocellular carcinoma. Surgery, 2014, 156(2), 270-279.
[http://dx.doi.org/10.1016/j.surg.2014.04.055] [PMID: 24953273]
[43]
Bancroft, J.; Gamble, M. Theory and practice of histopathological techniques.Elsevier health sciences: Philadelphia, 2008.
[44]
Reitman, S.; Frankel, S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am. J. Clin. Pathol., 1957, 28(1), 56-63.
[http://dx.doi.org/10.1093/ajcp/28.1.56] [PMID: 13458125]
[45]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, 95(2), 351-358.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[46]
Nishikimi, M.; Appaji, N.; Yagi, K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem. Biophys. Res. Commun., 1972, 46(2), 849-854.
[http://dx.doi.org/10.1016/S0006-291X(72)80218-3] [PMID: 4400444]
[47]
Bahri, M.; Hance, P.; Grec, S.; Quillet, M.C.; Trotin, F.; Hilbert, J.L.; Hendriks, T. A “novel” protocol for the analysis of hydroxycinnamic acids in leaf tissue of chicory (Cichorium intybus L., Asteraceae). ScientificWorldJ, 2012, 2012, 142983.
[http://dx.doi.org/10.1100/2012/142983] [PMID: 23304076]
[48]
Chkhikvishvili, I.; Kharebava, G. Chicoric and chlorogenic acids in plant species from Georgia. Appl. Biochem. Microbiol., 2001, 37, 188-191.
[http://dx.doi.org/10.1023/A:1002888016985]
[49]
Rossetto, M.; Lante, A.; Vanzani, P.; Spettoli, P.; Scarpa, M.; Rigo, A. Red chicories as potent scavengers of highly reactive radicals: A study on their phenolic composition and peroxyl radical trapping capacity and efficiency. J. Agric. Food Chem., 2005, 53(21), 8169-8175.
[http://dx.doi.org/10.1021/jf051116n] [PMID: 16218660]
[50]
Abd-Elbaset, M.; Mansour, A.M.; Ahmed, O.M.; Abo-Youssef, A.M. The potential chemotherapeutic effect of β-ionone and/or sorafenib against hepatocellular carcinoma via its antioxidant effect, PPAR-γ, FOXO-1, Ki-67, Bax, and Bcl-2 signaling pathways. Naunyn Schmiedebergs Arch. Pharmacol., 2020, 393(9), 1611-1624.
[http://dx.doi.org/10.1007/s00210-020-01863-9] [PMID: 32270258]
[51]
Hassan, H.A.; Yousef, M.I. Ameliorating effect of chicory (Cichorium intybus L.)-supplemented diet against nitrosamine precursors-induced liver injury and oxidative stress in male rats. Food Chem. Toxicol., 2010, 48(8-9), 2163-2169.
[http://dx.doi.org/10.1016/j.fct.2010.05.023] [PMID: 20478349]
[52]
Zhu, X.; Huang, F.; Xiang, X.; Fan, M.; Chen, T. Evaluation of the potential of chicoric acid as a natural food antioxidant. Exp. Ther. Med., 2018, 16(4), 3651-3657.
[http://dx.doi.org/10.3892/etm.2018.6596] [PMID: 30233721]
[53]
Hussein, O.E.; Hozayen, W.G.; Bin-Jumah, M.N.; Germoush, M.O.; Abd El-Twab, S.M.; Mahmoud, A.M. Chicoric acid prevents methotrexate hepatotoxicity via attenuation of oxidative stress and inflammation and up-regulation of PPARγ and Nrf2/HO-1 signaling. Environ. Sci. Pollut. Res. Int., 2020, 27(17), 20725-20735.
[http://dx.doi.org/10.1007/s11356-020-08557-y] [PMID: 32246423]
[54]
Karale, S.; Kamath, J.V. Effect of daidzein on cisplatin-induced hematotoxicity and hepatotoxicity in experimental rats. Indian J. Pharmacol., 2017, 49(1), 49-54.
[PMID: 28458422]
[55]
Keshk, W.A.; Soliman, N.A.; Ali, D.A.; Elseady, W.S. Mechanistic evaluation of AMPK/SIRT1/FXR signaling axis, inflammation, and redox status in thioacetamide-induced liver cirrhosis: The role of Cichorium intybus linn (chicory)-supplemented diet. J. Food Biochem., 2019, 43(8), e12938.
[http://dx.doi.org/10.1111/jfbc.12938] [PMID: 31368578]
[56]
Elgengaihi, S.; Mossa, A.T.; Refaie, A.A.; Aboubaker, D. Hepatoprotective efficacy of Cichorium intybus l. extract against carbon tetrachloride-induced liver damage in Rats. J. Diet. Suppl., 2016, 13(5), 570-584.
[http://dx.doi.org/10.3109/19390211.2016.1144230] [PMID: 26913368]
[57]
Berretta, M.; Rinaldi, L.; Di Benedetto, F.; Lleshi, A.; De Re, V.; Facchini, G.; De Paoli, P.; Di Francia, R. Angiogenesis inhibitors for the treatment of hepatocellular carcinoma. Front. Pharmacol., 2016, 7, 428.
[http://dx.doi.org/10.3389/fphar.2016.00428] [PMID: 27881963]
[58]
De Francesco, E.M.; Lappano, R.; Santolla, M.F.; Marsico, S.; Caruso, A.; Maggiolini, M. HIF-1α/GPER signaling mediates the expression of VEGF induced by hypoxia in breast cancer associated fibroblasts (CAFs). Breast Cancer Res., 2013, 15(4), R64.
[http://dx.doi.org/10.1186/bcr3458] [PMID: 23947803]
[59]
Choi, J.Y.; Jang, Y.S.; Min, S.Y.; Song, J.Y. Overexpression of mmp-9 and hif-1α in breast cancer cells under hypoxic conditions. J. Breast Cancer, 2011, 14(2), 88-95.
[http://dx.doi.org/10.4048/jbc.2011.14.2.88] [PMID: 21847402]
[60]
Kim, K.R.; Bae, J.S.; Choi, H.N.; Park, H.S.; Jang, K.Y.; Chung, M.J.; Moon, W.S. The role of serum response factor in hepatocellular carcinoma: An association with matrix metalloproteinase. Oncol. Rep., 2011, 26(6), 1567-1572.
[PMID: 21842128]
[61]
Cokakli, M.; Erdal, E.; Nart, D.; Yilmaz, F.; Sagol, O.; Kilic, M.; Karademir, S.; Atabey, N. Differential expression of Caveolin-1 in hepatocellular carcinoma: Correlation with differentiation state, motility and invasion. BMC Cancer, 2009, 9, 65.
[http://dx.doi.org/10.1186/1471-2407-9-65] [PMID: 19239691]
[62]
Salary, F.; Ramzani Ghara, A.; Ezzati Ghadi, F.; Bamdad, K. Antioxidant and hepatoprotective effects of irradiated chicory root on liver necrosis. Jentashapir J. Cell Mol. Biol., 2020, 11(2), e107180.
[http://dx.doi.org/10.5812/jjcmb.107180]
[63]
Laddha, A.P.; Murugesan, S.; Kulkarni, Y.A. In-vivo and in-silico toxicity studies of daidzein: An isoflavone from soy. Drug Chem. Toxicol., 2020, 15, 1-9.
[http://dx.doi.org/10.1080/01480545.2020.1833906] [PMID: 33059469]

Rights & Permissions Print Cite
Article Metrics
41
2
© 2024 Bentham Science Publishers | Privacy Policy