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American Journal of Cancer Prevention

ISSN (Print): 2328-7322

ISSN (Online): 2328-7314

Editor-in-Chief: Nabil Abdel-Hamid




Apple Cider Vinegar (A Prophetic Medicine Remedy) Protects against Nicotine Hepatotoxicity: A Histopathological and Biochemical Report

1Department of Anatomy, Faculty of Clinical Pharmacy, Taif University, KSA

2Department of Anatomy, Faculty of Medicine, Sohag University, Egypt

3Department of Pathology, Al-Ghad International Medical Sciences Colleges, Al-Madinah, KSA

4Department of Pathology, Faculty of Medicine, Sohag University, Egypt

5Department of Animal Production, Faculty of Agriculture, Jordan University, Jordan

6Department of Medical Biochemistry, Tanta Faculty of Medicine, Tanta University, Egypt

7Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia

8Department of Clinical Pathology, Faculty of Medicine, 6th October University, Cairo, Egypt

9Ph.D of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt

100Department of Internal Medicine, Tanta Faculty of Medicine, Tanta University, Egypt

111Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Egypt

American Journal of Cancer Prevention. 2015, 3(6), 122-127
doi: 10.12691/ajcp-3-6-4
Copyright © 2016 Science and Education Publishing

Cite this paper:
Nassar Ayoub Abdellatif Omar, Amal Nor Edeen Ahmad Allithy, Firas Mahmoud Faleh, Reham A. Mariah, Mongi Mohamed Ahmed Ayat, Sherine Ragab Shafik, Samah A. Elshweikh, Salah Mohamed El Sayed. Apple Cider Vinegar (A Prophetic Medicine Remedy) Protects against Nicotine Hepatotoxicity: A Histopathological and Biochemical Report. American Journal of Cancer Prevention. 2015; 3(6):122-127. doi: 10.12691/ajcp-3-6-4.

Correspondence to: Salah  Mohamed El Sayed, Department of Clinical Biochemistry and Molecular Medicine, Taibah Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia. Email:,


Nicotine is the most abundant component in cigarette smoking and is involved in the pathogenesis of lung cancer and increases the risk of developing hepatocellular carcinoma and liver cirrhosis. Prevention of nicotine-induced lung cancer and liver damage may be achieved via decreasing nicotine-induced pathological effects. Nicotine is metabolized in the liver. Natural diet contains a variety of compounds e.g. apple cider vinegar (ACV) that exhibits protective effects against different toxins. This study aims to investigate the effects of nicotine on the liver using morphometrical, histopathological and biochemical parameters and study the protective effect of ACV against toxicity of nicotine. Three groups of the male albino rat were used: untreated control group, nicotine treated group (4 mg/kg/day) while the third group received both ACV (2ml/kg/day) and nicotine (4 mg/kg/day). Treatment was given for 30 days. There was a significant increase in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) together with a damage and degeneration in the liver tissues of the nicotine treated groups. ACV administration to nicotine-treated rats showed near normal liver biochemical markers with reduction in the tissue damage associated with the nicotine administration. ACV administration to nicotine-treated rat ameliorated the decrease in the size of the hepatocytes nuclei. These results, along with previous observations, suggest that ACV may be useful in combating tissue injury resulting from nicotine toxicity. In prophetic medicine, Prophet Muhammad peace be upon him strongly recommended eating vinegar in the prophetic hadeeth: "vinegar is the best edible". Conclusion: These finding confirm that chronic nicotine administration causes harmful effects to the liver and suggest that ACV may be useful in combating tissue injury resulting from nicotine toxicity. Hence, the intake of ACV might suppress the toxicity and mutagenic activity of nicotine. ACV may protect against nicotine-induced carcinogenesis.



[1]  Baggio, B., Budakovic, A., Gambaro, G., 1998. Cardiovascular risk factors, smoking and kidney function. Nephrol., Dial. Transplant. 7, 2-5.
[2]  Benowitz, N.L., 1988. Pharmacological aspect of cigarette smoking and nicotine addiction. N.Engl.J.Med. 319, 1318-1330.
[3]  Boyle, P., 1997. Cancer, cigarette smoking and premature death in Europe: a review including the Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October 1996. Lung Cancer. 17, 1- 60.
[4]  Fagerstrom, K., 2002. The epidemiology of smoking: health consequences and benefits of cessation. Drugs. 62, 1-9.
[5]  Goette A., Lendeckel U., Kuchenbecker A., Bukowska A., Peters B., Klein H.U., Huth C., Rocken C., 2007. Cigarette smoking induces atrial fibrosis in humans via nicotine. Heart. 93, 1056-1063.
Show More References
[6]  Sekhon H., Proskocil B.J., Clark J.A., Spindel E.R., 2004. Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels. Eur. Respir. J. 23, 906-915.
[7]  Zhang, G, Kernan K.A., Thomas A., Collins S., Song Y., Li L., Zhu W., Leboeuf R.C., Eddy A.A., 2009. A novel signaling pathway: fibroblast nicotinic receptor alpha1 binds urokinase and promotes renal fibrosis. J. Biol. Chem. 284, 29050-29064.
[8]  Schievelbein H., Balfour D.J.K. 1984. Nicotine and the Tobacco Smoking Habit. Pergamon Press, Oxford. 1-15.
[9]  Benowitz, N.L., Porchet, H., Sheiner, L., Jacob, P., 1988b. Nicotine absorption and cardiovascular effects with smokeless tobacco use: Comparison with cigarettes and nicotine gum. Clinical Pharmacology and Therapeutics 4, 23-28.
[10]  Dani, J.A., Heinemann, S., 1996. Molecular and cellular aspects of nicotine abuse. Neuron. 16, 905–908.
[11]  Shivij SB, Camilo A, Moncada AB, Clarkson Jr, Salim M, 2006. Effect of nicotine on lung S-adenosylmethionine and development of pneumocystis pneumonia. J. Biol. Chem. 280(15), 15219-15228.
[12]  Suleyman H, Gumustekin K, Taysi S, Keles S, Oztasan N, Aktas O, et al., 2002. Beneficial effects of Hippophaerhamnoides L. on nicotine oxidative stress in rat blood compared with vitamin E. Biol Pharm Bull. 25, 1133-1136.
[13]  Van der Vaar, H., Postma, D.S., Timens, W., 2004. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 713-721.
[14]  Jung BH, Chung BC, Chung S, Shim C, 2001. Different pharmacokinetics of nicotine following intravenous administration of nicotine base and nicotine hydrogen tartarate in rats. J Control Release. 77, 183-190.
[15]  Kovacic, P., Cooksy, A., 2005. Iminium metabolism for nicotine toxicity and addiction: oxidative stress and electron transfer. Med. Hypotheses. 64, 104-111.
[16]  Ben Ahmed Halima, KhlifiSarra, Rtibi Kais, Elfazaa Salwa and Gharbi Najoua. 2010. Indicators of oxidative stress in weaning and pubertal rats following exposure to nicotine via milk. Hum ExpToxicol. 29 (6), 489-496.
[17]  Kalpana C, Menon VP., 2004. Protective effect of curcumin on circulatory lipid peroxidation and antioxidant status during nicotine-induced toxicity. Toxicol Mech Methods. 14, 339-343.
[18]  Muthukumaran S., Sdheer AR., MenonVP.,Nalini N., 2008. Protective effect of quercetin on nicotine-induced prooxidant and antioxidant imbalance and DNA. Toxicology. 243, 207-215.
[19]  Cashman, J.R., Park, S.B., Yang, Z.C., Wrighton, S.A., Jacob, P., Benowitz, N.L., 1992. Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N0-oxide. Chem. Res. Toxicol. 5, 639-646.
[20]  Yildiz D, 2004. Nicotine, its metabolism and an overview of its biological effects. Toxicol. 43, 619–632.
[21]  Wang, S. L.; He, X. Y. & Hong, J. Y., 2005. Human cytochrome p450 2s1: lack of activity in the metabolic activation of several cigarette smoke carcinogens and in the metabolism of nicotine. Drug Metab. Dispos., 33, 336-340.
[22]  Altamirano, R. Bataller., 2010. Cigarette smoking and chronic liver diseases. 59, 1159-1162.
[23]  Bataller, R,. 2006. Time to ban smoking in patients with chronic liver diseases. Hepatology. 44, 1394-1396.
[24]  Azzalini L., Ferrer E., Ramalho L.N., Moreno M., Dominguez M., Colmenero J., Peinado V.I., Barbera J.A., Arroyo V., Gines P., Caballeria J., Bataller R.,2010. Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats, Hepatology .51, 1567-1576.
[25]  Mori, M., Hara, M., Wada, I., Hara, T., Yamamoto, K., Honda, M., Naramoto, J., 2000. Prospective study of hepatitis B and C viral infections, cigarette smoking, alcohol consumption and other factors associated with hepatocellular carcinoma risk in Japan. Am. J. Epidemiol. 151,131-139.
[26]  Yu, M.W., Chiu, Y.H., Yang, S.Y., Santella, R.M., Chern, H.D., Liaw, Y.F., Chen, C.J., 1999. Cytochrome P450 1A1 genetic polymorphisms and risk of hepatocellular carcinoma among chronic hepatitis B carriers. Br. J. Cancer 80, 598-603.
[27]  Corrao, G., Lepore, A.R., Torchio, P., Valenti, M., Galatola, G., D’Amicis, A., Arico, S., Di Orio, F., 1994. The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption. A case-control study. Provincial Group for the Study of Chronic Liver Disease. Eur. J. Epidemiol. 10, 657-664.
[28]  Klatsky, A.L., Armstrong, M.A., 1992. Alcohol, smoking, coffee, and cirrhosis. Am. J. Epidemiol. 136, 1248-1257.
[29]  Yuen, S.T., Gogo Jr., A.R., Luck, I.C., Cho, C.H., Ho, J.C.I., Loh, T.T., 1995. The effect of nicotine and its interaction with carbon tetrachloride in the rat liver. Pharmacol. Toxicol. 77, 225-230.
[30]  Gamal H. El-Sokkary, Salvatore Cuzzocrea, Russel J. Reiter, 2007. Effect of chronic nicotine administration on the rat lung and liver: Beneficial role of melatonin Toxicology. 239, 60-67.
[31]  Sakakibara S, Yamauchi T, Oshima Y, Tsukamoto Y, Kadowaki T. (2006). Acetic acid activates hepatic AMPK and reduces hyperglycemia in diabetic KKA(y) mice. Biochem Biophys Res Commun 344:597-604.
[32]  Budak NH, Kumbul Doguc D, Savas CM, Seydim AC, Kok Tas T, Ciris MI, Guzel-Seydim ZB. 2011. Effects of apple cider vinegars produced with different techniques on blood lipids in high-cholesterol-fed rats. J Agric Food Chem.59:6638-6644.
[33]  Denis MC, Furtos A, Dudonné S, Montoudis A, Garofalo C, Desjardins Y, Delvin E, Levy E. 2013. Apple peel polyphenols and their beneficial actions on oxidative stress and inflammation. PLoS One 2013; 8:e53725.
[34]  Trochimowicz HJ, Kennedy Jr GL, Krivanek ND. Heterocyclic and miscellaneous nitrogen compounds. In: Clayton FE, ed. Patty’s Industrial hygiene and toxicology. 4th ed. New York, John Wiley & Sons, Inc.1994; IIE: 3374-9, 3489-91.
[35]  Giles AR., 1987. Guidelines for the use of animals in biomedical research. Thromb Haemost. 58, 1078-84.
[36]  Scherle, W. A simple method for volumetry of organs in quantitative stereology. Mikroskopie, 1970. v. 26, p. 57-63.
[37]  Bancroft, J. D. & Gamble, M. Theory and practice of histological techniques.5th. Ed. Edinburgh. Churchill Livingstone Pub. , 2002. pp 172-5, pp 593-620.
[38]  Takashi H., Masashi Y., Tadahito S., Mieko K. and Akira T, 2003. Intraportal nicotine infusion in rats decreases hepatic blood flow through endothelin-1 and both endothelin A and endothelin B receptors. Toxicology and Applied Pharmacology. 196, 1-10.
[39]  Hofffmann, D., Rivenson, A., Hecht, S.S., 1996. The biological significance of tobacco-specific N-nitrosamines: smoking and adenocarcinoma of the lung. Crit. Rev. Toxicol. 26:199-211.
[40]  V. Pachauri and S.J.S. Flora. 2013. Effect of nicotine pretreatment on arsenic-induced oxidative stress in male Wistar rats. Hum ExpToxicol. 32, 972-982.
[41]  Anandatheerthavarada, H.K., Williams, J.F., Wecker, L., 1993. The chronic administration of nicotine induces cytochrome P-450 in rat brain. J. Neurochem. 60, 1941-1944.
[42]  Guan, Z.Z., Yu, W.F., Nordberg, A., 2003. Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem. Int. 43: 243-249.
[43]  Hughes J.R., 1993.Treatment of smoking cessation in smokers with past alcohol/drug problems. J Subst Abuse Treat, 10:181-187.
[44]  Caraceni, P.; Domenicali, M.; Vendemiale, G.; Grattagliano, I.; Pertosa, A.; Nardo, B.; Morselli-Labate, A. M.; Trevisani, F.; Palasciano, G.; Altomare, E. & Bernardi, M. The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury. J. Surg. Res., 124:160-8, 2005.
[45]  Perlemuter, G.; Davit-Spraul, A.; Cosson, C.; Conti, M.; Bigorgne, A.; Paradis, V.; Corre, M. P.; Prat, L.; Kuoch, V.; Basdevant, A.; Pelletier, G.; Oppert, J. M. & Buffet, C. Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease. Liver Int., 25:946-53, 2005.
[46]  Wang, S. L.; He, X. Y. & Hong, J. Y. Human cytochrome p450 2s1: lack of activity in the metabolic activation of several cigarette smoke carcinogens and in the metabolism of nicotine. Drug Metab. Dispos., 33:336- 40, 2005.
[47]  Gamieldien, K. & Maritz, G. S. Postnatal expression of cytochrome P450 1A1, 2A3, and 2B1 mRNA in neonatal rat lung: influence of maternal nicotine exposure. Exp. Lung Res., 30:121-33, 2004.
[48]  Ashakumary, L. & Vijayammal, P. L. Effect of nicotine on lipoprotein metabolism in rats. Lipids, 32:311-5, 1997.
[49]  Miksys, S.; Hoffmann, E. & Tyndale, R. F. Regional and cellular induction of nicotine-metabolizing CYP2B1 in rat brain by chronic nicotine treatment. Biochem. Pharmacol., 59:1501-11, 2000.
[50]  Serobyan, N.; Orlovskaya, I.; Kozlov, V. & Khaldoyanidi, S. K. Exposure to nicotine during gestation interferes with the colonization of fetal bone marrow by hematopoietic stem/progenitor cells. Stem Cells Dev., 14:81-91, 2005.
[51]  Iba, M. M.; Fung, J.; Pak, Y. W.; Thomas, P. E.; Fisher, H.; Sekowski, A.; Halladay, A. K. & Wagner, G. C. Dose-dependent up-regulation of rat pulmonary, renal, and hepatic cytochrome P-450 (CYP) 1A expression by nicotine feeding. Drug Metab. Dispos., 27:977-82, 1999.
[52]  Kavitharaj, N. K. & Vijayammal, P. L. Nicotine administration induced changes in the gonadal functions in male rats. Pharmacology, 58:2-7, 1999.
[53]  Cooke, J. P. & Bitterman, H. Nicotine and angiogenesis: a new paradigm for tobacco-related diseases. Ann. Med., 36:33-40, 2004.
[54]  Borek C (2004) Dietary antioxidants and human cancer. Integr Cancer Ther 3: 333-341.
[55]  Davalos A, Bartolome B, Gomez-Cordoves C (2005) Antioxidant properties of commercial grape juices and vinegars. Food Chem 93: 325-330.
[56]  Seeram NP, Aviram M, Zhang Y, Henning SM, Feng L, et al. (2008) Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. J Agric Food Chem 56: 1415-1422.
[57]  Muslim Alqushiry. Sahih Muslim (2004) Berut, Hadeeth no. 2051, Asria library.
Show Less References


Graviola: A Systematic Review on Its Anticancer Properties

1School of Medicine, European University Cyprus, Nicosia, Cyprus

American Journal of Cancer Prevention. 2015, 3(6), 128-131
doi: 10.12691/ajcp-3-6-5
Copyright © 2016 Science and Education Publishing

Cite this paper:
Patrikios Ioannis, Stephanou Anastasis, Yiallouris Andreas. Graviola: A Systematic Review on Its Anticancer Properties. American Journal of Cancer Prevention. 2015; 3(6):128-131. doi: 10.12691/ajcp-3-6-5.

Correspondence to: Patrikios  Ioannis, School of Medicine, European University Cyprus, Nicosia, Cyprus. Email:


There has been an enormous interest in the literature that phyto-compounds have therapeutic and beneficial effects in various diseases including inflammatory associated arthritis, diabetes, hypertension, parasitic infections, and cancer. The leaves from the tropical tree Annona Muricata, also known as Graviola have been reported to have positive and effective properties against many of the above mentioned diseases. Cancer still remains the number one killer in the Western nations and most treatments for the disease rely on the use of chemotherapy that utilizes drugs that are also toxic against normal healthy cells. Thus, an alternative approach to anti-cancer therapies should involve the determination of novel drug targets that must be highly effective and specific against cancer development and growth. Additionally, the new generation novel drugs should be non-toxic to the host cells and affordable for the patients. This review summarizes the recent findings on the effects of Graviola tree extract as a novel anti-cancer agent for the treatment and prevention of cancers; a possible natural anti-cancer candidate agent in line with all the attributes pointed above.



[1]  Ignacimuthu S, Ayyanar M, Sivaraman S.K., Ethnobotanical investigations among tribes in Madurai district of Tamil Nadu (India). Journal of Ethnobiology and Ethnomedicine, 2. 1. 2006.
[2]  Elujoba A. A., Odeleye O. M., Ogunyemi C. M., Traditional medicine development for medical and dental primary health care delivery system in Africa. African Journal of Traditional, Complementary and Alternative Medicines, 2. 46. 2005.
[3]  Tomlinson T. R., Akerele O. Medicinal plants: their role in health and biodiversity. University of Pennsylvania Press, Philadelphia, 1998.
[4]  Gordon M. C., David J., Plants as a source of anti-cancer agents. Journal of Ethnopharmacology, 100. 72. 2005.
[5]  Gueritte F., Fahy J., The vinca alkaloids. In Anticancer Agents from Natural Products, edited by Cragg GM, Kingston DGI, Newman DJ. Brunner-Routledge Psychology Press, Taylor & Francis Group, Boca Raton, Chapter 7. 23. 2005.
Show More References
[6]  Patrikios Ioannis, Stephanou Anastasis, Yiallouris Andreas. Tripterygium Wilfordii Extract (Triptolide) and Amygdalin Promotes Cell death in Cancer Cells: True or a Myth. American Journal of Cancer Prevention Vol. 3, No. 4, 2015, pp 77-83.
[7]  Mishra, S.; Ahmad, S.; Kumar, N.; Sharma, B.K. Annona muricata(the cancer killer): A review. Glob. J. Pharm. Res. 2013, 2, 1613-1618.
[8]  Leboeuf, M.; Cavé, A.; Bhaumik, P.; Mukherjee, B.; Mukherjee, R. The phytochemistry of the annonaceae. Phytochemistry1980, 21, 2783-2813.
[9]  Adewole, S.O.; Caxton-Martins, E.A. Morphological changes and hypoglycemic effects of Annona muricataLinn. (Annonaceae) leaf aqueous extract on pancreatic B-cells of streptozotocin-treated diabetic rats. Afr. J. Biomed. Res. 2006, 9, 173-187.
[10]  De Souza, R.; Benassi, E.; da Silva, R.R.; Afonso, S.; Scarminio, I.S. Enhanced extraction yields and mobile phase separations by solvent mixtures for the analysis of metabolites in Annona muricata L. Leaves. J. Sep. Sci. 2009, 32, 4176-4185.
[11]  De Sousa, O.V.; Vieira, G.D.-V.; de Pinho, J.D.J.R.; Yamamoto, C.H.; Alves, M.S. Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricataL.leaves in animal models. Int. J. Mol. Sci. 2010, 11, 2067-2078.
[12]  Adewole, S.; Ojewole, J. Protective effects of Annona muricatalinn.(annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats. Afr. J. Tradit. Complement. Altern. Med. 2009, 6, 30-41.
[13]  Watt, J.M.; Breyer-Bnodwijk, M. The Medicinal and Poisonous Plants of Southern and Eastern Africa: Being an Account of Their Medicinal and Other Uses, Chemical Composition, Pharmacological Effects AodToricotogy in Man and Annimal; Lívingstone Ltd.: Edinburgh, UK; London, UK, 1962.
[14]  Jaramillo-Flores, M.; Hernandez-Sanchez, H. Thermal diffusivity of soursop (Annona muricata L.) pulp. J. Food Eng. 2000, 46, 139-143.
[15]  Wu, F.-E.; Gu, Z.-M.; Zeng, L.; Zhao, G.-X.; Zhang, Y.; McLaughlin, J.L. Sastrodihardjo, S. Two new cytotoxic monotetrahydrofuran annonaceous acetogenins, annomuricinsa and b, from the leaves of Annona muricata. J. Nat. Prod. 1995, 58, 830-836.
[16]  Vieira GHF, Mourão JA, Ângelo ÂM, Costa RA, Vieira SDF: Antibacterial effect (in vitro) of Moringaoleifera and Annona muricata against gram positive and gram negative bacteria. Rev Inst Med Trop Sao Paulo 2010, 52(3):129-132.
[17]  Heinrich M, Kuhnt M, Wright CW, Rimpler H, Phillipson JD, Schandelmaier A, Warhurst DC: Parasitological and microbiological evaluation of mixe Indian medicinal plants (Mexico). J Ethnopharmacol 1992, 36:81-85.
[18]  Antoun MD, Gerena L, Milhus WK: Screening of the flora of Puerto rico for potential antimalarial bioactives. Int J Pharmacol 1993, 31:255-258.
[19]  Baskar R, Rajeswari V, Kumar TS: In vitro antioxidant studies in leaves of annona species. Indian J ExpBiol 2007, 4:480-485.
[20]  Luna Jde S, De Carvalho JM, De Lima MR, Bieber LW, Bento Ede S, Franck X, Sant'ana AE: Acetogenins in Annona muricata L. (annonaceae) leaves are potent molluscicides. Nat Prod Res 2006, 20:253-257.
[21]  Rieser, M. J.; Gu, Z. M.; Fang, X. P.; Zeng, L.; Wood, K. V.; McLaughlin, J. L. Five novel mono-tetrahydrofuran ring acetogenins from the seeds of Annona muricata. J Nat. Prod. 1996, 59, 100.
[22]  Kim, G. S.; Zeng, L.; Alali, F.; Rogers, L. L.; Wu, F. E.; Sastrodihardjo, S.; McLaughlin, Muricoreacin and murihexocin C, mono-tetrahydrofuran acetogenins, from the leaves of Annona muricataJ. L. Phytochem. 1998, 49, 565.
[23]  Chang, F. R.; Wu, Y. C. Novel cytotoxic annonaceous acetogenins from Annona muricata.J Nat. Prod. 2001, 64, 925.
[24]  Liaw, C. C.; Chang, F. R.; Lin, C. Y.; Chou, C. J.; Chiu, H. F.; Wu, M. J.; Wu, Y. C. J New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. Nat. Prod. 2002, 65, 470.
[25]  Chang, F. R.; Liaw, C. C.; Lin, C. Y.; Chou, C. J.; Chiu, H. F.; Wu, Y. C. New adjacent Bis-tetrahydrofuran Annonaceous acetogenins from Annona muricata.Planta Medica2003, 69, 241.
[26]  Torres, M. P.; Rachagani, S.; Purohit, V.; Pandey, P.; Joshi, S.; Moore, E. D.; Johansson, S. L.; Singh, P. K.; Ganti, A. K.; Batra, S. K.Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett. 2012, 323, 29.
[27]  Hann J: A history of the Tumucua Indians and mission. Florida: University Press; 1996:13-21.
[28]  Pier O: Pacific island ecosystem at risk, “Result set for: Annonaceace Annona muricata”. United States Geological Survey and United States Forest Service: Pier species lists; 2008:8.
[29]  Rieser MJ, Kozlowski JF, Wood KV, McLaughlin J: Muricatacin: a simple biologically active acetogenin derivative from the seeds of Annona muricata (Annonaceae). Tetrahedron Lett 1991, 32:1137-1140.
[30]  CosmeKossouoh , Mansour Moudachirou , Victor Adjakidje , Jean-Claude Chalchat c& Gilles Figuérédo. Essential Oil Chemical Composition of Annona muricata L. Leaves fromBenin, Journal of Essential Oil Research(2007),19:4, 307-309,
[31]  Badrie N. and Schauss A.G. Soursop (Annona muricata L.): Composition, Nutritional Value, Medicinal Uses, and Toxicology, Bioactive Foods in Promoting Health, 2010, Ch. 39: 621-641
[32]  Sulaiman H, Roslida AH, Fezah O, Tan KL, Tor YS, Tan CI: Chemopreventive potential of Annona Muricata L Leaves on chemically-Induced skin papillomagenesis in mice. Asian Pac J Cancer Prev 2012, 13:2532-2533.
[33]  Leboeuf M, Cavé A, Bhaumik PK, Mukherjee B, Mukherjee R: The phytochemistry of the annonaceae. Phytochem 1982, 21:2783-2813.
[34]  Kossouoh C, Moudachirou M, Adjakidje V, Chalchat JC, Figuérédo G: Essential oil chemical composition of Annona muricata L. leaves from Benin. J Ess Oil Res 2007, 19:307-309.
[35]  Chang FR, Liaw CC, Lin CY, Chou CJ, Chiu HF, Wu YC: New adjacent bis-tetrahydrofuran annonaceous acetogenins from Annona muricata. Planta Med 2003, 69:241-246.
[36]  Ekaprasasti NR, Tuti SS, Retno WA: The breast of anticancer from leaf extract of Annona muricata againts cell line in t47d. Int J Applied SciTechnol 2012, 2(1):157-164.
[37]  Gajalakshmi S, Vijayalakshmi S, Devi. Rajeswari V:Phytochemical and pharmacological properties of Annona muricata: a review. Int J Pharm PharmSci 2012, 4(2):3-6.
[38]  Ragasa CY, Soriano G, Torres OB, Don MJ, Shen CC: Acetogenins from Annona muricata. Phcog J 2012, 32(4):32-37.
[39]  Dai Y, Hogan S, Schmelz EM, Ju YH, Canning C, Zhou K. Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression. Nutr Cancer. 2011; 63:795-801. [PubMed: 21767082].
[40]  Yu-Min Koa, Tung-Ying Wub, Yang-Chang Wub, Fang-RongChangb, Jinn-YuhGuhc,d,∗, Lea-Yea Chuange,∗Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-_-related pathways in MCF-7 cells. Journal of Ethnopharmacology. 137 (2011) 1283-1290.
[41]  Soheil Zorofchian Moghadamtousi, Hamed Karimian, Elham Rouhollahi, Mohammadjavad Paydar, Mehran Fadaeinasab, Habsah Abdul Kadir. Annona muricataleavesinduceG1 cell cyclearrest and apoptosis through mitochondria-mediated pathwayinhumanHCT-116 and HT-29 colon cancercells Journal of Ethnopharmacology 156 (2014) 277-289.
[42]  Constant Anatole Pieme, Santosh Guru Kumar, Mireille SylvianeDongmo, Bruno Moukette Moukette1, Fabrice Fekam Boyoum4, Jeanne YonkeuNgogang and Ajit Kumar Saxena. Antiproliferative activity and induction of apoptosis by Annona muricata (Annonaceae) bextract on human cancer cells. Pieme et al. BMC Complementary and Alternative Medicine 2014, 14:516.
[43]  Yang C1, Gundala SR1, Mukkavilli R2, Vangala S3, Reid MD4, Aneja R5.Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer.Carcinogenesis. 2015 Jun;36(6):656-65. doi: 10.1093/carcin/bgv046. Epub 2015 Apr 11.
[44]  Wang, L. Q., Min BS, Li Y, Nakamura N, Qin GW, Li CJ, Hattori M.. “Annonaceous acetogenins from the leaves of Annona montana.” Bioorg. Med. Chem. 2002;10(3):561-5.
[45]  Woo, M. H., Chung, S. O. & Kim, D. H. “Cis-annonacin and (2,4)-cis-and trans-isoannonacins: cytotoxic monotetrahydrofuran annonaceous acetogenins from the seeds of Annona cherimolia.” Arch. Pharm. Res. 1999; 22(5): 524-8.
[46]  Kim GS, Zeng L, Alali F, Rogers LL, Wu FE.“Muricoreacin and murihexocin c, mono-tetrahydrofuran acetogenins, from the leaves of Annona muricata.” Phytochemistry1998; 49(2): 565-571.
[47]  Zhao GX1, Rieser MJ, Hui YH, Miesbauer LR, Smith DL, McLaughlin JL. “Biologically active acetogenins from stem bark of Asiminatriloba.” Phytochemistry1993; 33(5): 1065-73.
[48]  Alali FQ1, Liu XX, McLaughlin JL. “Annonaceous acetogenins: Recent progress.” J. Nat. Prod. 1999; 62(3): 504-540.
[49]  Morre DJ, de Cabo R, Farley C, Oberlies NH, McLaughlin JL. “Mode of action of bullatacin, a potent antitumor acetogenin: inhibition of NADH oxidase activity of HeLa and HL-60, but not liver, plasma membranes.” Life Sci. 1995; 56(5): 343-8.
[50]  Nicholas H. Oberlies, Ching-jer Chang, and Jerry L. McLaughlin. “Structure-activity relationships of diverse annonaceousacetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells.” J. Med. Chem. 1997; 40(13): 2101-2106
[51]  González-Coloma A1, Guadaño A, de Inés C, Martínez-Díaz R, Cortes D. “Selective action of acetogenin mitochondrial complex I inhibitors.” Z. Naturforsch2002; 57(11-12): 1028-34.
[52]  J.B. Minari *, U. Okeke. Chemopreventive effect of Annona muricata on DMBA-induced cell proliferation in the breast tissues of female albino mice. The Egyptian Journal of Medical Human Genetics (2014) 15, 327–334.
[53]  Fernandes JV1, Cobucci RN, Jatobá CA, Fernandes TA, de Azevedo JW, de Araújo JM.The role of the mediators of inflammation in cancer development. PatholOncol Res. 2015 Jul;21(3):527-34.
[54]  Jeno Paul, R. Gnanam, R. M. Jayadeepa and L. Arul. Anti-Cancer Activity on Graviola, Exciting Medicinal Plant Extract vs Various Cancer Cell Lines and a Detailed Computational Study on its Potent Anti-Cancerous Leads. Current Topics in Medicinal Chemistry 2013. V.13:1666-1673:8.
[55]  Jayashree BS, Nigam S, Pai A, Patel HK, Reddy ND, Kumar N, Rao CM. Targets in anticancer research--A review. Indian J Exp Biol. 2015 Aug; 53(8):489-507.
[56]  C.W. Taylor, A.M. Kirby. Cardiac Side-effects From Breast Cancer Radiotherapy. Clinical Oncology 27 (2015) 621-629.
[57]  Christina H. Ruhlmann, Trine ZeebergIversen, MeenaOkera, Aida Muhic, Gunnar Kristensen Petra Feyer, Olfred Hansen. Multinational study exploring patients’ perceptions of side-effects induced by chemo-radiotherapy Radiother.Oncol.2015.09.014.
Show Less References


Meeting or Exceeding Physical Activity Guidelines is Associated with Reduced Risk for Cancer in Mexican-Americans

1Department of Epidemiology & Biostatistics, University of Texas Health Science Center at San Antonio-Laredo Campus, Laredo, TX (SW)

2Division of Epidemiology, University of Texas Health Science Center-Houston, School of Public Health, Brownsville Campus, Brownsville, TX (SPF, JBM)

3Division of Health Promotion and Health Behavior University of Texas Health Science Center-Houston, School of Public Health, Brownsville Campus, Brownsville, TX

American Journal of Cancer Prevention. 2016, 4(1), 1-7
doi: 10.12691/ajcp-4-1-1
Copyright © 2016 Science and Education Publishing

Cite this paper:
Shenghui Wu, Susan P. Fisher-Hoch, Belinda Reninger, Joseph B. McCormick. Meeting or Exceeding Physical Activity Guidelines is Associated with Reduced Risk for Cancer in Mexican-Americans. American Journal of Cancer Prevention. 2016; 4(1):1-7. doi: 10.12691/ajcp-4-1-1.

Correspondence to: Joseph  B. McCormick, Division of Epidemiology, University of Texas Health Science Center-Houston, School of Public Health, Brownsville Campus, Brownsville, TX (SPF, JBM). Email:


Background: Epidemiologic studies have shown that inadequate physical activity was associated with cancers in whites and other ethnic groups, but in Mexican-Americans data are limited. This study aimed to measure the association between physical activity and reported cancer risk in Mexican-Americans. Methods: Participants were drawn from the Cameron County Hispanic Cohort (n=3,391), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Physical activity was assessed using the International Physical Activity Questionnaire. Cancer was self-reported by the participants as being told by a health care provider that they had cancer. Results: Ninety-nine participants of the cohort (2.94%) reported a diagnosis of cancer. Compared to participants who did not meet US physical activity guidelines, subjects who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 METs) reduced their risk for cancer by 87% (OR=0.13; 95% CI: 0.03-0.54), and subjects with total minutes per week of moderate and vigorous/strenuous activity greater than 745 METs decreased cancer risk by 86% [odds ratio (OR)=0.14; 95% confidence interval (CI): 0.03-0.60] comparing with their counterparts, after adjusting for age, gender, body mass index, smoking and alcohol drinking status, education and total portions of fruit and vegetable intake. Conclusions: Meeting or exceeding recommended levels of moderate and vigorous physical activity was associated with a significantly reduced risk of reporting cancer by Mexican-Americans. Meeting or exceeding recommended levels of physical activity appears to be an effective target for cancer prevention and control among Mexican-Americans independent of BMI and other factors.



[1]  Ennis SR, Rios-Vargas M, Albert NG. The Hispanic Population: 2010. 2011. 2010 Census Briefs.
[2]  US Census Bureau. Current Population Survey, Annual Social and Economic Supplement, 2010. 2011.
[3]  American Cancer Society. Cancer Facts & Figures for Hispanics/Latinos 2012-2014 . 2012. Atlanta, American Cancer Society.
[4]  Lemanne D, Cassileth B, Gubili J, “The role of physical activity in cancer prevention, treatment, recovery, and survivorship”, Oncology (Williston Park), 27(6),580-585, 2013.
[5]  Gilliland FD, Li YF, Baumgartner K, Crumley D, Samet JM, “Physical activity and breast cancer risk in hispanic and non-hispanic white women”, Am J Epidemiol, 154(5),442-450, 2001.
Show More References
[6]  Slattery ML, Edwards S, Murtaugh MA, Sweeney C, Herrick J, Byers T et al., “Physical activity and breast cancer risk among women in the southwestern United States”, Ann Epidemiol, 17(5), 342-353, 2007.
[7]  Salazar-Martinez E, Lazcano-Ponce EC, Lira-Lira GG, Escudero-De los RP, Salmeron-Castro J, Larrea F et al., “Case-control study of diabetes, obesity, physical activity and risk of endometrial cancer among Mexican women”, Cancer Causes Control, 11(8), 707-711, 2000.
[8]  Fisher-Hoch SP, Rentfro AR, Salinas JJ, Perez A, Brown HS, Reininger BM et al., “Socioeconomic status and prevalence of obesity and diabetes in a Mexican American community, Cameron County, Texas, 2004-2007”, Prev Chronic Dis, 7(3),A53, 2010.
[9]  Fisher-Hoch SP, Vatcheva KP, Laing ST, Hossain MM, Rahbar MH, Hanis CL et al., “Missed opportunities for diagnosis and treatment of diabetes, hypertension, and hypercholesterolemia in a Mexican American population, Cameron County Hispanic Cohort, 2003-2008”, Prev Chronic Dis, 9,110298, 2012.
[10]  Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE et al., “International physical activity questionnaire: 12-country reliability and validity”, Med Sci Sports Exerc, 35(8), 1381-1395, 2003.
[11]  Gofin G, Shephard RJ, “Godin leisure-time exercise questionnaire”, Med Sci Sports Exerc, 29(6s),S36-S38, 2015.
[12]  Reininger BM, Mitchell-Bennett L, Lee M, Gowen RZ, Barroso CS, Gay JL et al., “Tu Salud, inverted exclamation markSi Cuenta!: Exposure to a community-wide campaign and its associations with physical activity and fruit and vegetable consumption among individuals of Mexican descent”, Soc Sci Med, 143,98-106, 2015.
[13]  Bauman A, Bull F, Chey T, Craig CL, Ainsworth BE, Sallis JF et al., “The International Prevalence Study on Physical Activity: results from 20 countries”, Int J Behav Nutr Phys Act, 6,21, 2009.
[14]  Hallal PC, Gomez LF, Parra DC, Lobelo F, Mosquera J, Florindo AA et al., “Lessons learned after 10 years of IPAQ use in Brazil and Colombia”, J Phys Act Health, 7 Suppl 2,S259-S264, 2010.
[15]  Rauh MJ, Hovell MF, Hofstetter CR, Sallis JF, Gleghorn A, “Reliability and validity of self-reported physical activity in Latinos”, Int J Epidemiol, 21(5),966-971, 1992.
[16]  Dang MM. Evidence of Reliability and Validity of IPAQ for Mexican-american Adults (Order No. 1470212). [ Dissertations & Theses @ University of Texas Health Science Center at Houston; 2009.
[17]  USDHHS. 2008 Physical activity guidelines for Americans. 2008. USDHHS.
[18]  Reininger BM, Wang J, Fisher-Hoch SP, Boutte A, Vatcheva K, McCormick JB, “Non-communicable diseases and preventive health behaviors: a comparison of Hispanics nationally and those living along the US-Mexico border”, BMC Public Health, 15,564, 2015.
[19]  US Department of Agriculture. Choose My Plate, Food Groups. 2013. US Department of Agriculture. [Accessed Sep. 9, 2015].
[20]  US Department of Agriculture. Choose My Plate, Vegetables. 2013. US Department of Agriculture. [Accessed Sep. 9, 2015].
[21]  Sun SS, Chumlea WC, Heymsfield SB, Lukaski HC, Schoeller D, Friedl K et al., “Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys”, Am J Clin Nutr, 77(2),331-340, 2003.
[22]  Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC, “Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man”, Diabetologia, 28(7),412-419, 1985.
[23]  Westerlind KC, “Physical activity and cancer prevention--mechanisms”, Med Sci Sports Exerc, 35(11),1834-1840, 2003.
[24]  Verkasalo PK, Thomas HV, Appleby PN, Davey GK, Key TJ, “Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom)”, Cancer Causes Control, 12(1),47-59, 2001.
[25]  McTiernan A, Ulrich C, Slate S, Potter J, “Physical activity and cancer etiology: associations and mechanisms”, Cancer Causes Control, 9(5), 487-509, 1998.
[26]  Thompson PD, Crouse SF, Goodpaster B, Kelley D, Moyna N, Pescatello L, “The acute versus the chronic response to exercise”, Med Sci Sports Exerc, 33(6 Suppl),S438-S445, 2001.
[27]  Shephard RJ, Verde TJ, Thomas SG, Shek P, “Physical activity and the immune system”, Can J Sport Sci, 16(3),169-185, 1991.
[28]  Ji LL, “Antioxidants and oxidative stress in exercise”, Proc Soc Exp Biol Med, 222(3),283-292, 1999.
[29]  Davis CD, Milner J, “Frontiers in nutrigenomics, proteomics, metabolomics and cancer prevention”, Mutat Res, 551(1-2),51-64, 2004.
[30]  Cai Z, Chiu JF, He QY, “Application of proteomics in the study of tumor metastasis”, Genomics Proteomics Bioinformatics, 2(3),152-166, 2004.
[31]  Harris H, “A long view of fashions in cancer research”, Bioessays, 27(8),833-838, 2005.
[32]  Stolk L, Perry JR, Chasman DI, He C, Mangino M, Sulem P et al., “Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways”, Nat Genet, 44(3),260-268, 2012.
[33]  Shen MR, Jones IM, Mohrenweiser H, “Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans”, Cancer Res, 58(4),604-608, 1998.
[34]  Airewele G, Adatto P, Cunningham J, Mastromarino C, Spencer C, Sharp M et al., “Family history of cancer in patients with glioma: a validation study of accuracy”, J Natl Cancer Inst, 90(7), 543-544, 1998.
[35]  Garza A, Vatcheva P, Pan JJ, Rahbar MH, Fallon MB, McCormick JB et al., “Liver and Other Gastrointestinal Cancers Are Frequent in Mexican Americans”, J Racial and Ethnic Health Disparities,1-10, 2014.
Show Less References