Flavonoides como agentes quimiopreventivos y terapéuticos contra el cáncer de pulmón

Albert Cabrera, Núria Mach


El objetivo de la presente revisión es estudiar la relación entre los flavonoides y el cáncer de pulmón, postulando que su consumo habitual en la dieta occidental podría resultar beneficioso para proteger a los pacientes contra el cáncer de pulmón. Se realizó una extensa búsqueda de publicaciones científicas recientes en las siguientes bases de datos electrónicas especializadas: PubMed central (PMC)-NCBI, Elsevier Journal, SciELO España, Scirus y Science Direct, incluyendo estudios en células, animales y humanos sobre el efecto de los flavonoides en la prevención y el desarrollo de cáncer de pulmón. Pese a que los estudios in vitro y en modelos animales muestran la capacidad potencial de los flavonoides para actuar contra diferentes tipos de cáncer, y en especial contra el riesgo de padecer cáncer de pulmón, la presencia de datos contradictorios en los estudios epidemiológicos y la falta de estudios clínicos en humanos actualmente impiden realizar recomendaciones dietéticas basadas en la evidencia científica para los pacientes con cáncer de pulmón. Así, los autores del presente artículo recomiendan seguir los consejos de las guías de alimentación saludable, las cuales promocionan el consumo de alimentos ricos en flavonoides y reflejan el conocimiento necesario para tratar a los pacientes con cáncer de pulmón.

Erratum in: Rev Esp Nutr Hum Diet. 2013;17(2):91-92

Link: http://www.renhyd.org/index.php/renhyd/article/view/6/17

Palabras clave

Flavonoides; Cáncer de pulmón; Quimioprevención

Texto completo:



Willett WC, Sacks F, Trichopoulou A, Drescher G, Ferro-Luzzi A, Helsing E, et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr. 1995;61(6 Suppl):S1402-6.

Bielsaki HK, Grimm P. En: Nutrición, texto y atlas. 1.a ed. Madrid: Panamericana; 2007.

Willett W. Nutrition and cancer: the search continues. Nutr Cancer.2008;60:557-9.

Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, Kampman E, et al. Nonlinear reduction in risk for colorectal cancer by fruit and vegetable intake based on meta-analysis of prospective studies. Gastroenterology. 2011;141:106-18.

Lunet N, Valbuena C, Vieira AL, Lopes C, David L, Carneiro F, et al. Fruit and vegetable consumption and gastric cancer by location and histological type: case-control and meta-analysis. Eur J Cancer Prev. 2007;16:312-27.

Pavia M, Pileggi C, Nobile CG, Angelillo IF. Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies. Am J Clin Nutr. 2006;83:1126-34.

Yang WS, Va P, Wong MY, Zhang HL, Xiang YB. Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies. Am J Clin Nutr. 2011;94:1575-83.

Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM. Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutr Cancer. 2009;61:598-606.

Butler LM, Wu AH. Green and black tea in relation to gynecologic cancers. Mol Nutr Food Res. 2011;55:931-40.

Mehta RG, Murillo G, Naithani R, Peng X. Cancer chemoprevention by natural products: how far have we come? Pharm Res. 2010;27:950-61.

Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP, Gescher AJ. Dietary polyphenolic phytochemicals —promising cancer chemopreventive agents in humans? A review of their clinical properties. Int J Cancer. 2007;120:451-8.

Mikkelsen TB, Osler M, Orozova-Bekkevold I, Knudsen VK, Olsen SF. Association between fruit and vegetable consumption and birth weight: a prospective study among 43,585 Danish women. Scand J Public Health. 2006;34:616-22.

Malinska D, Kiersztan A. Flavonoids —characteristics and significance for therapy. Postepy Biochem. 2004;50:182-96.

Meiyanto E, Hermawan A, Anindyajati A. Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents. Asian Pac J Cancer Prev. 2012;13:427-36.

Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett. 2008;269:315-25.

Ekstrom AM, Serafini M, Nyren O, Wolk A, Bosetti C, Bellocco R. Dietary quercetin intake and risk of gastric cancer: results from a population-based study in Sweden. Ann Oncol. 2011;22:438-43.

Yao H, Xu W, Shi X, Zhang Z. Dietary flavonoids as cancer prevention agents. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2011;29:1-31.

Birt DF, Hendrich S, Wang W. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther. 2001;90:157-77.

Neuhouser ML. Dietary flavonoids and cancer risk: evidence from human population studies. Nutr Cancer. 2004;50:1-7.

Tang NP, Zhou B, Wang B, Yu RB, Ma J. Flavonoids intake and risk of lung cancer: a meta-analysis. Jpn J Clin Oncol. 2009;39:352-9.

Arts IC. A review of the epidemiological evidence on tea, flavonoids, and lung cancer. J Nutr. 2008;138:1561-6.

Le Marchand L, Murphy SP, Hankin JH, Wilkens LR, Kolonel LN. Intake of flavonoids and lung cancer. J Natl Cancer Inst. 2000;92:154-60.

Garcia-Closas R, Agudo A, Gonzalez CA, Riboli E. Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain. Nutr Cancer. 1998;32:154-8.

Garcia-Tirado J, Rieger-Reyes C, Saz-Peiro P. Effect of flavonoids in the prevention of lung cancer: systematic review. Med Clin (Barc). 2012;139:1-6.

Knekt P, Jarvinen R, Seppanen R, Hellovaara M, Teppo L, Pukkala E, et al. Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. Am J Epidemiol. 1997;146:223-30.

Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P. Flavonol and flavone intake and the risk of cancer in male smokers (Finland). Cancer Causes Control. 2001;12:789-96.

Wang L, Lee IM, Zhang SM, Blumberg JB, Buring JE, Sesso HD. Dietary intake of selected flavonols, flavones, and flavonoid-rich foods and risk of cancer in middle-aged and older women. Am J Clin Nutr. 2009;89:905-12.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225-49.

Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765-81.

Egert S, Rimbach G. Which sources of flavonoids: complex diets or dietary supplements? Adv Nutr. 2011;2:8-14.

Williamson G, Sies H, Heber D, Keen CL, Macdonald IA, Actis-Goretta L, et al. Functional foods for health promotion: state-of-the-science on dietary flavonoids. Extended abstracts from the 12th Annual Conference on Functional Foods for Health Promotion, April 2009. Nutr Rev. 2009;67:736-43.

Mlodzinska E. Survey of plant pigments: molecular and environmental determinants of plant colors. Act Biol Crac Ser Bot. 2009;51:7-16.

Mo Y, Nagel C, Taylor LP. Biochemical complementation of chalcone synthase mutants defines a role for flavonols in functional pollen. Proc Natl Acad Sci U S A. 1992;89:7213-7.

Wiseman BR, Snook M, Widstrom NW. Feeding responses of the corn ear worm larvae (Lepidoptera: Noctuidae) on corn silks of varying flavone content. J Econ Entomol. 1996;89:1040-4.

Dixon RA, Steele CL. Flavonoids and isoflavonoids —a gold mine for metabolic engineering. Trends Plant Sci. 1999;4:394-400.

Grotewold E. The science of flavonoids. New York: Springer; 2006.

Di Carlo G, Mascolo N, Izzo AA, Capasso F. Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sci. 1999;65:337-53.

Bhagwat S, Haytowitz DB, Holden JM. USDA Database for the flavonoid content of selected foods. Baltimore: US Department of Agriculture; 2011.

Chabot GG, Touil YS, Pham MH, Dauzonne D. Flavonoids in cancer prevention and therapy: chemistry, pharmacology, mechanisms of action, and perspectives for cancer drug discovery. En: Alaoui-Jamali M, editor. Alternative and complementary therapies for cancer. New York: Springer; 2010.

Grassi D, Desideri G, Croce G, Tiberti S, Aggio A, Ferri C. Flavonoids, vascular function and cardiovascular protection. Curr Pharm Des. 2009;15:1072-84.

Huang Y, Tsang SY, Yao X, Chen ZY. Biological properties of baicalein in cardiovascular system. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5:177-84.

Andres A, Donovan SM, Kuhlenschmidt MS. Soy isoflavones and virus infections. J Nutr Biochem. 2009;20:563-9.

Mota KS, Dias GE, Pinto ME, Luiz-Ferreira A, Souza-Brito AR, Hiruma-Lima CA, et al. Flavonoids with gastroprotective activity. Molecules. 2009;14:979-1012.

Cheong H, Ryu SY, Oak MH, Cheon SH, Yoo GS, Kim KM. Studies of structure activity relationship of flavonoids for the anti-allergic actions. Arch Pharm Res. 1998;21:478-80.

Stoclet JC, Chataigneau T, Ndiaye M, Oak MH, El Bedoui J, Chataigneau M, et al. Vascular protection by dietary polyphenols. Eur J Pharmacol. 2004;500:299-313.

Gilani AH, Janbaz KH, Shah BH. Quercetin exhibits hepatoprotective activity in rats. Biochem Soc Trans. 1997;25:S619.

Majumdar S, Srirangam R. Potential of the bioflavonoids in the prevention/treatment of ocular disorders. J Pharm Pharmacol. 2010;62:951-65.

Spencer JP. The impact of fruit flavonoids on memory and cognition. Br J Nutr. 2010;104:40-7.

Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev. 2011;5:1-12.

Liao YC, Shih YW, Chao CH, Lee XY, Chiang TA. Involvement of the ERK signaling pathway in fisetin reduces invasion and migration in the human lung cancer cell line A549. J Agric Food Chem. 2009;57:8933-41.

Hsiao YC, Kuo WH, Chen PN, Chang HR, Lin TH, Yang WE, et al. Flavanone and 2’-OH flavanone inhibit metastasis of lung cancer cells via down-regulation of proteinases activities and MAPK pathway. Chem Biol Interact. 2007;167:193-206.

Cai X, Ye T, Liu C, Lu W, Lu M, Zhang J, et al. Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells. Toxicol In Vitro. 2011;25:1385-91.

Moon YJ, Wang X, Morris ME. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro. 2006;20:187-210.

Nguyen TT, Tran E, Ong CK, Lee SK, Do PT, Huynh TT, et al. Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK. J Cell Physiol. 2003;197:110-21.

Nguyen TT, Tran E, Nguyen TH, Do PT, Huynh TH, Huynh H. The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis. 2004;25:647-59.

Kuo PC, Liu HF, Chao JI. Survivin and p53 modulate quercetin-induced cell growth inhibition and apoptosis in human lung carcinoma cells. J Biol Chem. 2004;279:55875-85.

Kosmider B, Wojcik I, Osiecka R, Bartkowiak J, Zyner E, Ochocki J, et al. Enhanced P53 and BAX gene expression and apoptosis in A549 cells by cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP. Invest New Drugs. 2005;23:287-97.

Schwarz D, Kisselev P, Roots I. CYP1A1 genotype-selective inhibition of benzo[a]pyrene activation by quercetin. Eur J Cancer. 2005;41:151-8.

Chen W, Wang X, Zhuang J, Zhang L, Lin Y. Induction of death receptor 5 and suppression of survivin contribute to sensitization of TRAIL-induced cytotoxicity by quercetin in non-small cell lung cancer cells. Carcinogenesis. 2007;28:2114-21.

Leung HW, Lin CJ, Hour MJ, Yang WH, Wang MY, Lee HZ. Kaempferol induces apoptosis in human lung non-small carcinoma cells accompanied by an induction of antioxidant enzymes. Food Chem Toxicol. 2007;45:2005-13.

Chen LG, Hung LY, Tsai KW, Pan YS, Tsai YD, Li YZ, et al. Wogonin, a bioactive flavonoid in herbal tea, inhibits inflammatory cyclooxygenase-2 gene expression in human lung epithelial cancer cells. Mol Nutr Food Res. 2008;52:1349-57.

Lee HJ, Lee EO, Ko SG, Bae HS, Kim CH, Ahn KS, et al. Mitochondria-cytochrome C-caspase-9 cascade mediates isorhamnetin-induced apoptosis. Cancer Lett. 2008;270:342-53.

Khan N, Mukhtar H. Cancer and metastasis: prevention and treatment by green tea. Cancer Metastasis Rev. 2010;29:435-45.

Du G, Han G, Zhang S, Lin H, Wu X, Wang M, et al. Baicalin suppresses lung carcinoma and lung metastasis by SOD mimic and HIF-1alpha inhibition. Eur J Pharmacol. 2010;630:121-30.

Hung JY, Hsu YL, Ko YC, Tsai YM, Yang CJ, Huang MS, et al. Didymin, a dietary flavonoid glycoside from citrus fruits, induces Fas-mediated apoptotic pathway in human non-small-cell lung cancer cells in vitro and in vivo. Lung Cancer. 2010; 68:366-74.

Anso E, Zuazo A, Irigoyen M, Urdaci MC, Rouzaut A, Martinez-Irujo JJ. Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism. Biochem Pharmacol. 2010;79:1600-9.

Hsu HS, Lin JH, Huang WC, Hsu TW, Su K, Chiou SH, et al. Chemoresistance of lung cancer stemlike cells depends on activation of Hsp27. Cancer. 2011;117:1516-28.

Ravichandran N, Suresh G, Ramesh B, Siva GV. Fisetin, a novel flavonol attenuates benzo(a)pyrene-induced lung carcino-genesis in Swiss albino mice. Food Chem Toxicol. 2011;49:1141-7.

Hasani A, Leighl N. Classification and toxicities of vascular disrupting agents. Clin Lung Cancer. 2011;12:18-25.

Jin CY, Park C, Hwang HJ, Kim GY, Choi BT, Kim WJ, et al. Naringenin up-regulates the expression of death receptor 5 and enhances TRAIL-induced apoptosis in human lung cancer A549 cells. Mol Nutr Food Res. 2011;55:300-9.

Lopez-Lazaro M. Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anticancer Agents. 2002;2:691-714.

Cutler GJ, Nettleton JA, Ross JA, Harnack LJ, Jacobs DR Jr, Scrafford CG, et al. Dietary flavonoid intake and risk of cancer in postmenopausal women: the Iowa Women’s Health Study. Int J Cancer. 2008;123:664-71.

Mursu J, Nurmi T, Tuomainen TP, Salonen JT, Pukkala E, Voutilainen S. Intake of flavonoids and risk of cancer in Finnish men: The Kuopio Ischaemic Heart Disease Risk Factor Study. Int J Cancer. 2008;123:660-3.

Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, et al. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am J Clin Nutr. 2010;91:722-8.

Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, et al. Plasma isoflavones and the risk of lung cancer in women: a nested case-control study in Japan. Cancer Epidemiol Biomarkers Prev. 2011;20:419-27.

DOI: http://dx.doi.org/10.14306/renhyd.16.4.61

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Abreviatura: Rev Esp Nutr Hum Diet

DOI revista: 10.14306/renhyd



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