Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

Zhang,Qiang; Yang,Jie; Wang,Jun

doi:10.3892/ol.2016.5291

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

Authors:
- Qiang Zhang
- Jie Yang
- Jun Wang
View Affiliations

Affiliations: Department of General Surgery, Xiangyang Hospital, Affiliated Hospital of Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
Published online on: October 19, 2016 https://doi.org/10.3892/ol.2016.5291
Pages: 4767-4772

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Liver cancer is one of the leading causes of cancer‑associated mortality worldwide. Due to changes in lifestyle and daily exposure to various chemicals, which may lead to chemical intoxication, liver cancer has become a prominent disease in humans. Chemical‑induced carcinogenesis in experimental animals has become a reliable model for the investigation of liver cancer‑associated biological alterations that may mimic human hepatic cancer. Liver cancer in BALB/c mice was induced by administering diethylnitrosamine (DN) in drinking water for 6 weeks. Luteolin (LUT) is a flavone that is found in the leaves of the majority of spice‑associated plants. In the present study, 20 µg/kg of body weight LUT was administered intraperitoneally every alternate day to treat the DN‑induced liver cancer in mice. LUT improved the host system by modifying the levels of α‑fetoprotein, enzymatic antioxidants, such as superoxide dismutase and catalase, marker enzymes, such as AST and ALT, and lipid peroxides in the plasma or liver tissue. LUT also reduced the levels of glutathione and the inflammatory cytokines interleukin‑2 and interferon‑γ in the plasma or liver tissue. These findings augmented the treatment against liver cancer and supported the effective anticancer activity of LUT against DN‑induced liver carcinogenesis in mice.

View Figures

View References

1	Altekruse SF, McGlynn KA and Reichman ME: Hepatocellular carcinoma incidence, mortality and survival trends in the United States from 1995 to 2005. J Clin Oncol. 27:1485–1491. 2009. View Article : Google Scholar : PubMed/NCBI
2	Fattovich G, Stroffolini T, Zagni I and Donato F: Hepatocellular carcinoma and cirrhosis: Incidence and risk factors. Gastroenterology. 127(5): Suppl 1. S35–S50. 2004. View Article : Google Scholar : PubMed/NCBI
3	Faloppi L, Scartozzi M, Maccaroni E, Di Pietro Paolo M, Berardi R, Del Prete M and Cascinu S: Evolving strategies for the treatment of hepatocellular carcinoma: From clinical-guided to molecularly-taylored therapeutic options. Cancer Treat Rev. 37:169–177. 2011. View Article : Google Scholar : PubMed/NCBI
4	Borzio M, Fargion S, Borzio F, Fracanzani AL, Croce AM, Stroffolini T, Oldani S, Cotichini R and Roncalli M: Impact of large regenerative, low grade and high grade dysplastic nodules in hepatocellular carcinoma development. J Hepatol. 39:208–214. 2003. View Article : Google Scholar : PubMed/NCBI
5	Pawlik TM, Poon RT, Abdalla EK, Ikai I, Nagorney DM, Belghiti J, Kianmanesh R, Ng IO, Curley SA, Yamaoka Y, et al: Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: Results of a multicenter study. Surgery. 137:403–410. 2005. View Article : Google Scholar : PubMed/NCBI
6	Irtan S, Chopin-Laly X, Ronot M, Faivre S, Paradis V and Belghiti J: Complete regression of locally advanced hepatocellular carcinoma induced by sorafenib allowing curative resection. Liver Int. 31:740–743. 2011. View Article : Google Scholar : PubMed/NCBI
7	Petersen FB, Buckner CD, Appelbaum FR, Clift RA, Sanders JE, Bensinger WI, Storb R, Witherspoon RP, Sullivan KM and Bearman SI: Busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for marrow transplantation in patients with advanced hematological malignancies: A phase I study. Bone Marrow Transplant. 4:617–623. 1989.PubMed/NCBI
8	Senthilkumar S, Devaki T, Manohar BM and Babu MS: Effect of squalene on cyclophosphamide-induced toxicity. Clin Chim Acta. 364:335–342. 2006. View Article : Google Scholar : PubMed/NCBI
9	Clemens MR, Ladner C, Schmidt H, Ehninger G, Einsele H, Bühler E, Waller HD and Gey KF: Decreased essential antioxidants and increased lipid hydroperoxides following high-dose radiochemotherapy. Free Radic Res Commun. 7:227–232. 1989. View Article : Google Scholar : PubMed/NCBI
10	Hosakote YM, Liu T, Castro SM, Garofalo RP and Casola A: Respiratory syncytial virus induces oxidative stress by modulating antioxidant enzymes. Am J Respir Cell Mol Biol. 41:348–357. 2009. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Li J, Cao L, Xu W and Yin Z: Circulating tumor cells in hepatocellular carcinoma: Detection techniques, clinical implications and future perspectives. Semin Oncol. 39:449–460. 2012. View Article : Google Scholar : PubMed/NCBI
12	Lopez-Lazaro M: Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem. 9:31–59. 2009. View Article : Google Scholar : PubMed/NCBI
13	Cai X, Lu W, Ye T, Lu M, Wang J, Huo J, Qian S, Wang X and Cao P: The molecular mechanism of luteolin-induced apoptosis is potentially related to inhibition of angiogenesis in human pancreatic carcinoma cells. Oncol Rep. 28:1353–1361. 2012.PubMed/NCBI
14	Merfort I, Heilmann J, Hagedorn-Leweke U and Lippold BC: In vivo skin penetration studies on chamomile flavones. Pharmazie. 49:509–511. 1994.PubMed/NCBI
15	Plaschke K: Composition comprising one or more flavonoids, method of obtaining such composition and use there of as UV-absorbing agent. US Patent 6,409,996 B1. Filed November 19, 1998; issued June 25. 2002.
16	Graefe EU, Derendorf H and Veit M: Pharmacokinetics and bioavailability of the flavonols quercetin in humans. Int J Clin Pharmacol Ther. 37:219–233. 1999.PubMed/NCBI
17	Ohkawa H, Ohishi N and Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 95:351–358. 1979. View Article : Google Scholar : PubMed/NCBI
18	Ellman GL: Tissue sulfhydryl groups. Arch Biochem Biophys. 82:70–77. 1959. View Article : Google Scholar : PubMed/NCBI
19	Morota K, Komori M, Fujinami R, Yamada K, Kuribayashi K, Watanabe N, Sokoll LJ, Elliott D, Chan DW, Martens F, et al: Improvement and multicenter evaluation of the analytical performance of an automated chemiluminescent immunoassay for alpha fetoprotein. Int J Biol Markers. 27:39–46. 2012. View Article : Google Scholar : PubMed/NCBI
20	Rice-Evans CA, Miller NJ and Paganga G: Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 20:933–956. 1996. View Article : Google Scholar : PubMed/NCBI
21	Halliwell B and Gutteridge JM: Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet. 1:1396–1397. 1984. View Article : Google Scholar : PubMed/NCBI
22	Senthilkumar S, Ebenezar KK, Sathish V, Yogeeta S and Devaki T: Modulation of tissue defense system by squalene in cyclophosphamide induced toxicity in rats. Arch Med Sci. 2:94–100. 2006.
23	Quinlan GJ and Gutteridege JM: Hydroxyl radical generation by the tetracycline antibodies with free radical damage to DNA, lipids, carbohydrates in the presence of iron and copper salts. Free Radic Biol Med. 5:341–348. 1988. View Article : Google Scholar : PubMed/NCBI
24	Van Poppel G, Verhoeven DT, Verhagen H and Goldbohm RA: Brassica vegetables and cancer prevention. Epidemiology and mechanisms. Adv Exp Med Biol. 472:159–168. 1999. View Article : Google Scholar : PubMed/NCBI
25	Østergaard H, Tachibana C and Winther JR: Monitoring disulfide bond formation in the eukaryotic cytosol. J Cell Biol. 166:337–345. 2004. View Article : Google Scholar : PubMed/NCBI
26	Senthilkumar S, Yogeeta SK, Subashini R and Devaki T: Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats. Chem Biol Interact. 160:252–260. 2006. View Article : Google Scholar : PubMed/NCBI
27	Tafazoli S and O'Brien PJ: Peroxidases: A role in the metabolism and side effects of drugs. Drug Discov Today. 10:617–625. 2005. View Article : Google Scholar : PubMed/NCBI
28	Trevisani F, D'Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P, Domenicalli M, De Notariis S, Roda E and Bernardi M: Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: Influence of HBsAg and anti- HCV status. J Hepatol. 34:570–575. 2001. View Article : Google Scholar : PubMed/NCBI
29	Wright LM, Kreikemeier JT and Fimmel CJ: A concise review of serum markers for hepatocellular cancer. Cancer Detect Prev. 31:35–44. 2007. View Article : Google Scholar : PubMed/NCBI
30	Chiappini F: Circulating tumor cells measurements in hepatocellular carcinoma. Int J Hepatol. 2012:6848022012. View Article : Google Scholar : PubMed/NCBI
31	Yang Gui-zhen: Boundary immunology. Beijing: Science Press; 2002, View Article : Google Scholar
32	Tagawa M: Cytokine therapy for cancer. Curr Pharm Des. 6:681–699. 2000. View Article : Google Scholar : PubMed/NCBI
33	Kusters S, Gantner F, Künstle G and Tiegs G: Interferon-ã plays a critical role in T cell-dependent liver injury in mice initiated by concanavalin A. Gastroenterology. 111:462–471. 1996. View Article : Google Scholar : PubMed/NCBI
34	Haqqi TM, Anthony DD, Gupta S, Ahmad N, Lee MS, Kumar GK and Mukhtar H: Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc Natl Acad Sci USA. 96:4524–4529. 1999. View Article : Google Scholar : PubMed/NCBI