Liposome Encapsulated Astaxanthin Altered Biochemical Profile In Diethylnitrosamine (DEN) Induced Hepato Carcinoma On Swiss Albino Mice
Abstract
Cancer is a disease in which a group of abnormal cells grow uncontrollably by disregarding the normal rules of cell division. Across several cancers, Hepatocellular carcinoma (HCC) is one of the most aggressive cancers in worldwide. It is held responsible for up to 1 million deaths globally per annum. HCC is an inflammation-related cancer, as a chronic inflammatory state is necessary for cancer appearance. In this study, the drug astaxanthin and encapsulated astaxanthin was tested against HCC. Mice were divided into 7 groups; Group I: control, Group II: DEN induced, Group III: DEN + 50 mg/kg astaxanthin, Group IV: DEN + 100 mg/kg astaxanthin, Group V: DEN + 50 mg/kg encapsulated astaxanthin, Group VI: DEN + 100 mg/kg encapsulated astaxanthin, Group VII: DEN + 10 mg/kg sorafenib. Regular diet was given. Body weight, Food intake, water intake was noted. Other biochemical parameters such as ALP, AST, Albumin, proteins and TNF-α was determined. Finally, the liver was removed from each mice of different group by sacrificing them and histopathology was done. In vivo evaluation in mice models showed significant antitumor activities by both encapsulated and non-encapsulated astaxanthin at 100 mg/kg as compared with the control, DEN induced group and positive drug sorafenib. This research suggested that encapsulated astaxanthin can also be used as chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).
Keywords:
Hepatocellular carcinoma (HCC), Astaxanthin, Diethylnitrosoamine (DEN), Tumor Necrosis Factor-alpha (TNF-α).DOI
https://doi.org/10.25004/IJPSDR.2020.120406References
Papas AM. Diet and anti-oxidant status, in Anti-oxidant Status. Diet, Nutrition and Health, Papas, A.M., Ed., CRC Press, Boca Raton, Florida, 1998, chap. 5.
Chesson A, Collins A. Assessment of the role of diet in cancer prevention. Cancer Lett. 1997;114:281-237.
Lee BM, Park KK. Beneficial and adverse effects of chemopreventive agents. Mutat Res. 2003;265:523-524.
Sporn MB, Suh N. Chemoprevention: an essential approach to controlling cancer. Nature Rev Cancer. 2002;2:529-537.
Wargovich MJ. Experimental evidence for cancer preventive elements in food. Cancer Lett. 1997;114:1-11.
Pashkow FJ, Watumull DG, Campbell CL. Astaxanthin: A novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol. 2008;101:58D-68D.
Miki W, Yamaguchi K, Konosu S. Comparison of carotenoids in the ovaries of marine fish and shellfish. Comp Biochem Physiol B. 1982;71(1):7-11.
Guerin M, Huntley ME, Olaizola M. Haematococcus astaxanthin: Applications for human health and nutrition. Trends Biotechnol. 2003;21:210-216.
Zhang XS, Zhang X, Zhou ML, Zhou XM, Li N, Li W, et al. Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage. J Neurosurg. 2014a;121:42-54.
Ikeda Y, Tsuji S, Satoh A, Ishikura M, Shirasawa T, Shimizu T. Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells. J Neurochem. 2008;107:1730-1740.
Liu X, Shibata T, Hisaka S, Osawa T. Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism. Brain Res. 2009;1254:18-27.
Shen H, Kuo CC, Chou J, Delvolve A, Jackson SN, Post J, et al. Astaxanthin reduces ischemic brain injury in adult rats. FASEB J. 2009;23:1958-1968.
Wu Q, Zhang XS, Wang HD, Zhang X, Yu Q, Li W, et al. Astaxanthin activates nuclear factor erythroid-related factor 2 and the antioxidant responsive element (Nrf2-ARE) pathway in the brain after subarachnoid hemorrhage in rats and attenuates early brain injury. Mar Drugs. 2014;12:6125-6141.
Zhang XS, Zhang X, Wu Q, Li W, Zhang QR, Wang CX, et al. Astaxanthin alleviates early brain injury following subarachnoid hemorrhage in rats: Possible involvement of Akt/bad signaling. Mar Drugs. 2014b;12:4291-4310.
Lu YP, Liu SY, Sun H, Wu XM, Li JJ, Zhu L. Neuroprotective effect of astaxanthin on H(2)O(2)-induced neurotoxicity in vitro and on focal cerebral ischemia in vivo. Brain Res. 2010;1360:40-48.
Gross GJ, Lockwood SF. Cardioprotection and myocardial salvage by a disodium disuccinate astaxanthin derivative (Cardax). Life Sci. 2004;75:215-224.
Lauver DA, Lockwood SF, Lucchesi BR. Disodium Disuccinate Astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion. J Pharmacol Exp Ther. 2005;314:686-692.
Fassett RG, Coombes JS. Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol. 2009;5:333-342.
Kavitha K, Kowshik J, Kishore TK, Baba AB, Nagini S. Astaxanthin inhibits NF-kappaB and Wnt/beta-catenin signaling pathways via inactivation of Erk/MAPK and PI3K/Akt to induce intrinsic apoptosis in a hamster model of oral cancer. Biochim Biophys Acta. 2013;1830:4433-4444.
Tanaka T, Morishita Y, Suzui M, Kojima T, Okumura A, Mori H. Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin. Carcinogenesis. 1994;15:15-19.
Nagendraprabhu P, Sudhandiran G. Astaxanthin inhibits tumor invasion by decreasing extracellular matrix production and induces apoptosis in experimental rat colon carcinogenesis by modulating the expressions of ERK-2, NFkB and COX-2. Investig. New Drugs. 2011;29:207-224.
Yasui Y, Hosokawa M, Mikami N, Miyashita K, Tanaka T. Dietary astaxanthin inhibits colit is and colit is-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chem Biol Interact. 2011;193:79-87.
Zhang X, Zhao WE, Hu L, Zhao L, Huang J. Carotenoids inhibit proliferation and regulate expression of peroxisome proliferatorsactivated receptor gamma (PPARgamma) in K562 cancer cells. Arch Biochem Biophys. 2011;512:96-106.
Song XD, Zhang JJ, Wang MR, Liu WB, Gu XB, Lv CJ. Astaxanthin induces mitochondria-mediated apoptosis in rat hepatocellular carcinoma CBRH-7919 cells. Biol Pharm Bull. 2011;34:839-844.
Song X, Wang M, Zhang L, Zhang J, Wang X, Liu W, et al. Changes in cell ultrastructure and inhibition of JAK1/STAT3 signaling pathway in CBRH-7919 cells with astaxanthin. Toxicol Mech Methods. 2012;22:679-686.
Keating GM. Sorafenib: A Review in Hepatocellular Carcinoma. Target Oncol. 2017;12(2):243-253.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69-90.
Merle P, Mornex F. Medical therapies for hepatocellular carcinoma. Cancer Radiother. 2011;15:28-31.
Villanueva A, Hernandez-Gea V, Llovet JM. Medical therapies for hepatocellular carcinoma: A critical view of the evidence. Nat Rev Gastroenterol Hepatol. 2013;10:34-42.
Lin MV, King LY, Chung RT. Hepatitis C virus-associated cancer. Annu Rev Pathol. 2015;10:345-370.
Markowitz GJ, Michelotti GA, Diehl AM, Wang XF. Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma. Sci Bull (Beijing). 2015;60:762-772.
Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Fushiya N, et al. Comparison of the prognostic value of inf lammation-based prognostic scores in patients with hepatocellular carcinoma. Br J Cancer. 2012;107:988-993.
Proctor MJ, Morrison DS, Talwar D, Balmer SM, O’Reilly DS, Foulis AK, et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: A glasgow inflammation outcome study. Br J Cancer. 2011;104:726-734.
Lasry A, Ben-Neriah Y. Senescence-associated inflammatory responses: Aging and cancer perspectives. Trends Immunol. 2015;36:217-228.
Xu J, Yin Z, Cao S, Gao W, Liu L, Yin Y, et al. Systematic review and meta-analysis on the association between IL-1B polymorphisms and cancer risk. PLoS One. 2013;8:e63654.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436-444.
Chu WM. Tumor necrosis factor. Cancer Lett. 2013;328:222-225.
Engelmann H, Holtmann H, Brakebusch C, Avni YS, Sarov I, Nophar Y, et al. Antibodies to a soluble form of a tumor necrosis factor (TNF) receptor have TNF-like activity. J Biol Chem. 1990;265:14497-14504.
Mocellin S, Rossi CR, Pilati P, Nitti D. Tumor necrosis factor, cancer and anti-cancer therapy. Cytokine Growth Factor Rev. 2005;16:35-53.
Zins K, Abraham D, Sioud M, Aharinejad S. Colon cancer cell-derived tumor necrosis factor-alpha mediates the tumor growth-promoting response in macrophages by up-regulating the colony-stimulating factor-1 pathway. Cancer Res. 2007;67:1038-1045.
Hagemann T, Robinson SC, Schulz M, Trümper L, Balkwill FR, Binder C. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases. Carcinogenesis. 2004;25:1543-1549.
Egberts JH, Cloosters V, Noack A, Schniewind B, Thon L, Klose S, et al. Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 2008;68:1443-1450.
Ferrajoli A, Keating MJ, Manshouri T, Giles FJ, Dey A, Estrov Z, et al. The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia. Blood. 2002;100:1215-1219.
Aroucha DC, do Carmo RF, Moura P, Silva JL, Vasconcelos LR, Cavalcanti MS, et al. High tumor necrosis factor-α/interleukin-10 ratio is associated with hepatocellular carcinoma in patients with chronic hepatitis C. Cytokine. 2013;62:421-425.
Wang YY, Lo GH, Lai KH, Cheng JS, Lin CK, Hsu PI. Increased serum concentrations of tumor necrosis factor-alpha are associated with disease progression and malnutrition in hepatocellular carcinoma. J Chin Med Assoc. 2003;66:593-598.
Avrămescu CS, Comănescu V, Popescu SN, Turculeanu A, Bălăşoiu M, Popescu CF, et al. Correlations among the serum levels of some interleukins and the histopathological aspects in chronic viral hepatitis C. Rom J Morphol Embryol. 2008;49:57-62.
Chiu CH, Chang CC, Lin ST, Chyau CC, Peng RY. Improved Hepatoprotectivity effect of Liposome-encapsulated astaxanthin in lipopolysaccharide-induced acute hepatotoxicity. Inte J Mol sci. 2016;17:1-17.
Suganya V, Anuradha V, Syed Ali M, Sangeetha P, Bhuvana P. Microencapsulation and characterization of astaxanthin prepared using different agents. Res J Chem Sci. 2017;7:1-10.
Mross K, Frost A, Steinbild S, Hedbom S, Büchert M, Fasol U, et al. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012;18:2658-2667.
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.
Wei Z, Doria C, Liu Y. Targeted therapies in the treatment of advanced hepatocellular carcinoma. Clin Med Insights Oncol. 2013;7:87-102.
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF. SHARP Investigators Study Group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378-390.
Sheppard K, Kinross KM, Solomon B, Pearson RB, Phillips WA. Targeting PI3 kinase/AKT/mTOR signaling in cancer. Crit Rev Oncog. 2012;17:69-95.
Dahmani R, Just PA, Perret C. The Wnt/beta-catenin pathway as a therapeutic target in human hepatocellular carcinoma. Clin Res Hepatol Gastroenterol. 2011;35:709-713.
Göbel T, Blondin D, Kolligs F, Bölke E, Erhardt A. Current therapy of hepatocellular carcinoma with special consideration of new and multimodal treatment concepts. Dtsch Med Wochenschr. 2013;138:1425-1430.
Chabner BA, Roberts TG. Timeline: Chemotherapy and the war on cancer. Nat Rev Cancer. 2005;5:65-71.
Mousa B. Sorafenib in the treatment of advanced hepatocellular carcinoma. The Saudi J Gastroenterol. 2008;14:40-42.
Desar IM, Mulder SF, Stillebroer AB, van Spronsen DJ, van der Graaf WT, Mulders PF, et al. The reverse side of the victory:flare up of symptoms after discontinuation of sunitinib orsorafenib in renal cell cancer patients, A report of three cases. Acta Oncol. 2009;48:927-931.
Kitada N, Kanamori K, Konishi A, Tanaka S, Suginoshita Y, Inokuma T, et al. Analysis of factors affecting the duration of treatment with sorafenib in patients with hepatocellular carcinoma. Gan To Kagaku Ryoho. 2013;40:479-482.
Nakayama M, Arai Y, Nishimura K. Side effects of sorafenib and countermeasures. Hinyokika Kiyo. 2012;58:635-637.
Li J, Wang F, Xia Y, Dai W, Chen K, Li S, et al. Astaxanthin pretreatment attenuates hepatic ischemia reperfusion-induced apoptosis and autophagy via the ROS/MAPK pathway in mice. Mar Drugs. 2015a;13:3368-3387.
Li J, Xia Y, Liu T, Wang J, Dai W, Wang F, et al. Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis. PLoS one. 2015b;10:e120440.
Shen M, Chen K, Lu J, Cheng P, Xu L, Dai W, et al. Protective effect of astaxanthin on liver fibrosis through modulation of TGF-beta1 expression and autophagy. Mediat Inflamm. 2014;2014:1-10.
Regnier P, Bastias J, Rodriguez-Ruiz V, Caballero-Casero N, Caballo C, Sicilia D, et al. Astaxanthin from Haematococcus pluvialis prevents oxidative stress on human endothelial cells without toxicity. Mar Drugs. 2015;13:2857-2874.
Zhang L, Wang H. Multiple mechanisms of anti-cancer effects exerted by astaxanthin. Mar Drugs. 2015;13:4310-4330.
Chekanov K, Lobakova E, Selyakh I, Semenova L, Sidorov R, Solovchenko A. Accumulat ion of astaxanthin by a new Haematococcus pluvialis strain BM1 from the white sea coastal rocks (Russia). Mar Drugs. 2014;12:4504-4520.
Guo SX, Zhou HL, Huang CL, You CG, Fang Q, Wu P, et al. Astaxanthin attenuates early acute kidney injury following severe burns in rats by ameliorating oxidative stress and mitochondrial-related apoptosis. Mar Drugs. 2015;13:2105-2123.
Jyonouchi H, Sun S, Iijima K, Gross MD. Antitumor activity of astaxanthin and its mode of action. Nutr Cancer. 2000;36:59-65.
Kowshik J, Baba AB, Giri H, Deepak Reddy G, Dixit M, Nagini S. Astaxanthin inhibits JAK/STAT-3 signaling to abrogate cell proliferation, invasion and angiogenesis in a hamster model of oral cancer. PLoS ONE. 2014;9:e109114.
Rao AR, Sindhuja HN, Dharmesh SM, Sankar KU, Sarada R, Ravishankar GA. Effective inhibition of skin cancer, tyrosinase, and anti-oxidative properties by astaxanthin and astaxanthin esters from the green alga Haematococcus pluvialis. J Agric Food Chem. 2013;61:3842-3851.
Nakao R, Nelson OL, Park JS, Mathison BD, Thompson PA, Chew BP. Effect of dietary astaxanthin at different stages of mammary tumor initiation in BALB/c mice. Anticancer Res. 2010;30:2171-2175.
Tripathi DN, Jena GB. Astaxanthin intervention ameliorates cyclophosphamide-induced oxidative stress, DNA damage and early hepatocarcinogenesis in rat: Role of Nrf2, p53, p38 and phase-II enzymes. Mutat Res. 2010;696:69-80.
Andrei S, Cernea C, Taulescu M, Catoi M. Effects of astaxanthin supplementation on chemically induced tumorigenesis in Wistar rats. Acta Vet Scand. 2014;54(50):15-18.
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