Abo Bibliothek: Guest
Digitales Portal Digitale Bibliothek eBooks Zeitschriften Referenzen und Berichte Forschungssammlungen
Journal of Environmental Pathology, Toxicology and Oncology
Impact-faktor: 1.625 5-jähriger Impact-Faktor: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Druckformat: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019030301
pages 239-251

Anti-Inflammatory and Apoptotic Signaling Effect of Fucoxanthin on Benzo(A)Pyrene-Induced Lung Cancer in Mice

Weiwei Chen
Respiratory Department, Cangzhou People's Hospital, Cangzhou, Hebei, 061000, China
Hongjing Zhang
Respiratory Department, Cangzhou People's Hospital, Cangzhou, Hebei, 061000, China
Yue Liu
Respiratory Department, Cangzhou People's Hospital, Cangzhou, Hebei, 061000, China


Fucoxanthin, a potent carotenoid present in various natural sources especially from seaweeds; it exhibits several biological effects like anti-neoplastic, anti-mutagenic, anti-diabetic, anti-obesity and anti-inflammatory actions. Fucoxanthin role in chemoprevention of lung cancer in mouse model induced using benzo(a)pyrene [B(a)P] has been presented here. Oral administration of fucoxanthin with and without B(a)P were studied, the results from our study shows that fucoxanthin significantly decreased tumor progression in mice exposed to B(a)P, the obtained data were correlated with increased antioxidant, apoptosis and decreased tumour marker and anti-apoptotic molecules. With respect to apoptosis, fucoxanthin treated animals shows increased apoptosis compared to tumor induced mice by increased expression of caspase 9 and 3 and decreased expression of anti-apoptotic Bcl2 protein. Finally, histopathological and immuno histochemical analysis also revealed that fucoxanthin shows potent anticancer agent by bringing back the damaged tissue treated with B(a)P and also decreases the expression of PCNA in cancer induced mice. The anticancer effect of fucoxanthin may be attributed by several independent mechanisms which play a important roles in the prevention of cancer development, there is also substantial evidences to show that fucoxanthin acts indirectly by increasing the antioxidant capacity of affected tissue and prepared to cope up with oxidative stress which is proved in our study. Thus from our study it is clearly established that fucoxanthin act as a persuasive anticancer drug against lung cancer.


  1. Kruger S, Buck AK, Mottaghy FM, Hasenkamp E, Pauls S, Schumann C, Wibmer T, Merk T, Hombach V, Reske SN. Detection of bone metastases in patients with lung cancer: 99mTc-MDP planar bone scintigraphy, F-fluoride PET or 18F-FDG PET/CT. Eur J Nucl Med Mol Imag. 2009;36:1807-12.

  2. Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P; Members of IASLC Staging Committee. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4:568-77.

  3. She J, Yang P, Hong Q, Bai C. Lung cancer in China: chal-lenges and interventions. Chest J. 2013;143:1117-26.

  4. Gutschner T, Hammerle M, EiBmann M, Hsu J, Kim Y, 15. Hung G, Revenko A, Aran G, Stentrup M, GroB M. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73:1180-9.

  5. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9-29.

  6. Zhang Z, Lee JC, Lin L, Olivas V, Au V, LaFram-boise T, Abdel-Rahman M, Wang X, Levine AD, Rho JK. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 18. 2012;44:852-60.

  7. Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su W-C, Wang M, Sun Y. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX- Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012;13:528-38.

  8. Bittoni MA, Harris RE, Clinton SK, Focht BC. The 21. relationships between c-reactive protein, smoking, and lung cancer mortality in the Third National Health and Nutrition Examination Survey. Cancer Res. 2013;73:3632.

  9. Moolgavkar SH, Holford TR, Levy DT, Kong CY, Foy M, Clarke L, Jeon J, Hazelton WD, Meza R, Schultz F. Impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975 C2000. J Natl Cancer Inst. 2012;104:541-8.

  10. Wang C, Dai Y, Feng G, He R, Yang W, Li D, Zhou X, Zhu L, Tan L. Addition of porphyrins to cigarette filters to reduce the levels of benzo [a] pyrene (B[a]P) and to-bacco-specific N-nitrosamines (TSNAs) in mainstream cigarette smoke. J Agr Food Chem. 2011;59:7172-7.

  11. World Health Organization. Standard operating procedure for determination of tobacco-specific nitrosamines in mainstream cigarette smoke under ISO and intense smoking conditions: 2014. Available from: https://apps. who.int/iris/handle/10665/136000?show=full.

  12. Le Calvez F, Mukeria A, Hunt JD, Kelm O, Hung RJ, Taniere P, Brennan P, Boffetta P, Zaridze DG, Hainaut P. TP53 and KRAS mutation load and types in lung cancers in relation to tobacco smoke: distinct patterns in never, former, and current smokers. Cancer Res. 2005; 65:5076-83.

  13. Hussain SP, Amstad P, Raja K, Sawyer M, Hofseth L, Shields PG, Hewer A, Phillips DH, Ryberg D, Haugen A. Mutability of p53 hotspot codons to benzo (a) pyrene diol epoxide (BPDE) and the frequency of p53 mutations in nontumorous human lung. Cancer Res. 2001;61:6350-5.

  14. Zuo J, Brewer DS, Arlt VM, Cooper CS, Phillips DH. Benzo pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcino-genesis in mice. BMC Genom. 2014;15:880.

  15. Maeda H, Hosokawa M, Sashima T, Takahashi N, Kawada T, Miyashita K. Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells. Int J Mol Med. 2006;18:147-52.

  16. Nishino H. Cancer prevention by carotenoids. Mutat Res. 1998;402:159-63.

  17. Rengarajan T, Rajendran P, Nandakumar N, Balasu-bramanian M, Nishigaki I. Cancer preventive efficacy of marine carotenoid fucoxanthin: cell cycle arrest and apoptosis. Nutrients. 2013 Dec;5(12):4978-89.

  18. Martin L. Fucoxanthin and its metabolite fucoxanthinol in cancer prevention and treatment. Marine Drugs. 2015 Aug;13(8):4784-98.

  19. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47:469-74.

  20. Sinha KA. Colorimetric assay of catalase. Anal Biochem. 1972;47:389-94.

  21. Mohandas J, Marshall JJ, Duggin GG, Horvath JS, Tiller DJ. Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer. Cancer Res. 1984;44:5086-91.

  22. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130-39.

  23. Carlberg I, Mannervik B. Purification and characterization of the flavoenzyme glutathione reductase from rat liver. J Biol Chem. 1975;250:5475-80.

  24. Jollow D, Mitchell J, Zampaglione NA, Gillette J. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology. 1974;11:151-69.

  25. Devasagayam TP, Tarachand U. Decreased lipid peroxidation in rat kidney during gestation. Biochem Biophys Res Commun. 1987;145:134-8.

  26. Buening MK, Chang RL, Huang MT, Fortner JG, Wood AW, Conney AH. Activation and inhibition of benzo (a) pyrene and aflatoxin B1 metabolism in human liver microsomes by naturally occurring flavonoids. Cancer Res. 1981;41:67-72.

  27. King EJ. Practical clinical enzymology. London: Nostrand;1965. p. 121-38.

  28. Rosalki SB, Rau D. Serum -glutamyltranspeptidase activity in alcoholism. Clin Chim Acta. 1972;39:41-7.

  29. Luly P, Barnabei O, Tria E. Hormonal control in vitro of plasma membrane-bound (Na+-K+)-ATPase of rat liver. Biochem Biophys Acta. 1972;282:447-52.

  30. Hosokawa M, Okada T, Mikami N, Konishi I, Miyashita K. Bio-functions of marine carotenoids. Food Sci Biotech. 2009;18:1-11.

  31. Yan X, Chuda Y, Suzuki M, Nagata T. Fucoxanthin as the major antioxidant in Hijikia fusiformis, a common edible seaweed. Biosci Biotechnol Biochem. 1999;63:605-7.

  32. Dembitsky VM, Maoka T. Allenic and cumulenic lipids. Prog Lipid Res. 2007;46:328-75.

  33. Achir N, Randrianatoandro VA, Bohuon P, Laffargue A, Avallone S. Kinetic study of P-carotene and lutein degradation in oils during heat treatment. Eur J Lipid Sci Tech. 2010;112:349-61.

  34. Zhao D, Kim SM, Pan CH, Chung D. Effects of heating, aerial exposure and illumination on stability of fucoxanthin in canola oil. Food Chem. 2014;145:505-13.

  35. Sangeetha RK, Bhaskar N, Baskaran V. Comparative effects of beta-carotene and fucoxanthin on retinol deficiency induced oxidative stress in rats. Mol Cell Biochem. 2009;331:59-67.

  36. Ramakrishnan G, Balaji Raghavendran HR, Vinodhkumar R, Devaki T. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem Biol Interact. 2006;161:104-14.

  37. Kim SH, Kwack SJ, Lee BM. Lipid peroxidation, anti-oxidant enzymes, and benzo[a]pyrene-quinones in the blood of rats treated with benzo[a]pyrene. Chem Biol Interact. 2000;127:139-50.

  38. Ramakrishnan G, Augustine TA, Jagan S, Vinodhkumar R, Devaki T. Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Exp Oncol. 2007;29:39-44.

  39. Bagchi D, Bagchi M, Stohs JS, Das KD, Ray DS, Kuszynski AC, Joshi SS, Pruess GH. Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology. 2000; 148:187-97.

  40. Li S, Yan T, Yang QJ, Oberley DT, Oberley WL. The role of cellular glutathione peroxidase redox regulation in the suppression of tumor cell growth by manganese superoxide dismutase. Cancer Res. 2000;60:3927-39.

  41. Gaetani GF, Galiano S, Canepa L, Ferraris AM, Kirkman HN. Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes. Blood. 1989;73:334-39.

  42. Balkwill F, Joffroy C. TNF: a tumor-suppressing factor or a tumor-promoting factor? Future Oncol. 2010;6:1833-36.

  43. Rose-John S, Schooltink H. Cytokines are a therapeutic target for the prevention of inflammation-induced cancers. Recent Results Cancer Res. 2007;174:57-66.

  44. Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Asokkumar S, Naveenkumar C. Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model. Inflamm Res. 2012;61:1169-75.

  45. Kai H, Kitadai Y, Kodama M, Cho S, Kuroda T, Ito M. Involvement of proinflammatory cytokines IL-1P and IL-6 in progression of human gastric carcinoma. Anticancer Res. 2005;25:709-13.

  46. Ola MS, Nawaz M, Ahsan, H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem. 2011;351:41-58.

  47. Adams JM, Cory S. Bcl-2-regulated apoptosis: mechanism and therapeutic potential. Curr Opin Immunol. 2007;19:488-96.

  48. Wang J, Chen S, Xu S, Yu X, Ma D, Hu X, Cao X. In vivo induction of apoptosis by fucoxanthin, a marine carotenoid, associated with down-regulating STAT3/EGFR signaling in sarcoma 180 (S180) xenograft-bearing mice. Mar Drugs. 2012;10:2055-68.

  49. Hosokawa M, Kudo M, Maeda H, Kohno H, Tanaka T, Miyashita K. Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARy ligand, troglitazone, on colon cancer cells. Biochim Biophys Acta. 2004;1675:113-19.

  50. Konishi I, Hosokawa M, Sashima T, Kobayashi H, Miyashita K. Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi induce apoptosis in human leukemia, breast and colon cancer cells. Comp Biochem Physiol C. 2006;142:53-59.

  51. Nakazawa Y, Sashima T, Hosokawa M, Miyashita K. Comparative evaluation of growth inhibitory effect of stereoisomers of fucoxanthin in human cancer cell lines. J Funct Foods. 2009;1:88-97.

  52. Ganesan P, Noda K, Manabe Y, Ohkubo T, Tanaka Y, Maoka T, Sugawara T, Hirata T. Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells. Biochim Biophys Acta. 2011;1810:497-503.

  53. Zhang Z, Zhang P, Hamada M, Takahashi S, Xing G, Liu J, Sugiura N. Potential chemoprevention effect of dietary fucoxanthin on urinary bladder cancer EJ-1 cell line. Oncol Rep. 2008;20:1099-103.

  54. Li J, Tharappel JC, Han SG, Cantor AH, Lee EY, Gairola CG, Glauert HP. Inhibition of cigarette smoke-induced lung cell proliferation by dietary selenium in mice. FASEB J. 2009;23.

  55. Kunnumakkar, AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates anti-tumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007;67(8):3853-61.

  56. Kamaraj S, Ramakrishnan G, Anandakumar P, Jagan S, Devaki T. Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice. Invest New Drugs. 2009;27:214-22.

  57. Tanaka T, Kohno H, Shimada R, Kagami S, Yamaguchi F, Kataoka S, Ariga T, Murakami A, Koshimizu K, Ohigashi H. Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats. Carcinogenesis. 2009;21:1183-89.

  58. Yoshitani SI, Tanaka T, Kohno H, Takashima S. Chemoprevention of azoxymethane-induced colon carcinogenesis by dietary capsaicin and roenone. Int J Oncol. 2001;19:929-39.

  59. Haddad AQ, Venkateswaran V, Viswanathan L, Teahan SJ, Fleshner NE, Klotz LH. Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer Prostatic Dis. 2006;9:68-76.

  60. Khan N, Afaq F, Syed DN, Mukhtar H. Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells. Carcinogenesis. 2008;29:1049-56.

Articles with similar content:

Hypoxia-Inducible Factor-lα Increase is an Early and Sensitive Marker of Lung Cells Responding to Benzo[a]Pyrene
Journal of Environmental Pathology, Toxicology and Oncology, Vol.31, 2012, issue 4
Olga Mavrofrydi , Panagiota Papazafiri
Change in Nicotine-Induced VEGF, PGE2 AND COX-2 Expression Following COX Inhibition in Human Oral Squamous Cancer
Journal of Environmental Pathology, Toxicology and Oncology, Vol.31, 2012, issue 4
Bita Sedaghati, Masoumeh Esfahani, Mona Salimi, Mehrangiz Esfandiary, Hamid Reza Aslani, Narcis Habibzadeh, Sepideh Arbabi Bidgoli, Mohammad Hossein Ghahremani, Amir Amanzadeh
Curcumin Augments the Efficacy of Antitumor Drugs Used in Leukemia by Modulation of Heat Shock Proteins Via HDAC6
Journal of Environmental Pathology, Toxicology and Oncology, Vol.33, 2014, issue 3
Apurba Mukherjee, Raj Biswas, Madhumita Roy, Sutapa Mukherjee, Jaydip Biswas, Ruma Sarkar
VEGF Antibody Plus Cisplatin Reduces Angiogenesis and Tumor Growth in a Xenograft Model of Ovarian Cancer
Journal of Environmental Pathology, Toxicology and Oncology, Vol.29, 2010, issue 1
Putul Maity, Sonali Ghosh
Dietary Nanosized Lactobacillus plantarum Enhances the Anticancer Effect of Kimchi on Azoxymethane and Dextran Sulfate Sodium−Induced Colon Cancer in C57BL/6J Mice
Journal of Environmental Pathology, Toxicology and Oncology, Vol.35, 2016, issue 2
Kwang-Won Lee, Kun-Young Park, Hyun Ah Lee, Hyunung Kim