Chemopreventive Effect of Amorphophallus campanulatus (Roxb.) blume tuber against aberrant crypt foci and cell proliferation in 1, 2-dimethylhydrazine induced colon carcinogenesis

  • Ansil, Puthuparampil Nazarudeen (Biochemistry and Pharmacognosy Research Laboratory, School of Biosciences, Mahatma Gandhi University) ;
  • Prabha, Santhibhavan Prabhakaran (Biochemistry and Pharmacognosy Research Laboratory, School of Biosciences, Mahatma Gandhi University) ;
  • Nitha, Anand (Biochemistry and Pharmacognosy Research Laboratory, School of Biosciences, Mahatma Gandhi University) ;
  • Latha, Mukalel Sankunni (Biochemistry and Pharmacognosy Research Laboratory, School of Biosciences, Mahatma Gandhi University)
  • 발행 : 2013.09.30


Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.


  1. Bird RP, Good CK (2000). The significance of aberrant crypt foci in understanding the pathogenesis of colon cancer. Toxicol Lett, 112, 395-402.
  2. Ansil PN, Jazaira V, Prabha SP, Nitha A, Latha MS (2013). Amorphophallus campanulatus (roxb.) Blume. tuber ameliorates hepatic oxidative stress during colon carcinogenesis induced by 1, 2 dimethylhydrazine. Int J Pharm Pharm Sci, 5, 366-71.
  3. Ansil PN, Nitha A, Prabha SP, et al (2011). Protective effect of Amorphophallus campanulatus (Roxb.) Blume. tuber against thioacetamide induced oxidative stress in rats. Asian Pac J Trop Med, 4, 870-7.
  4. Aranganathan S, Panneer SJ, Nalini N (2009). Hesperetin exerts dose dependent chemopreventive effect against 1,2-dimethyl hydrazine induced rat colon carcinogenesis. Invest New Drugs, 27, 203-13.
  5. Beers RF Jr, Sizer IW (1952). A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem, 195, 133-40.
  6. Bird RP (1987). Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Lett, 37, 147-51.
  7. Boateng J, Verghese M, Chawan CB, et al (2006). Red palm oil suppresses the formation of azoxymethane (AOM) induced aberrant crypt foci (ACF) in Fisher 341 male rats. Food Chem Toxicol, 44, 1667-73.
  8. Bravo R, Frank R, Blundell PA, et al (1987). Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature, 326, 515-7.
  9. Carlberg I, Mannervik B (1985). Glutathione reductase. Methods Enzymol, 113, 484-90.
  10. Chung MY, Lim TG, Lee KW (2013). Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development. World J Gastroenterol, 19, 984-93.
  11. Das D, Mondal S, Roy SK, et al (2009). Isolation and characterization of a heteropolysaccharide from the corm of Amorphophallus campanulatus. Carbohydr Res, 344, 2581-5.
  12. Das U (2002). A radical approach to cancer. Med Sci Monit, 8, 79-92.
  13. Ellman GL (1959). Tissue sulfhydryl groups. Arch Biochem Biophys, 82, 70-7.
  14. Fernandes CR, Turatti A, Gouvea DR, et al (2011). The protective role of Lychnophora ericoides Mart. (Brazilian arnica) in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis. Nutr Cancer, 63, 593-9.
  15. Hamiza OO, Rehman MU, Tahir M, et al (2012). Amelioration of 1, 2 Dimethylhydrazine (DMH) induced colon oxidative stress, inflammation and tumor promotion response by tannic acid in Wistar rats. Asian Pac J Cancer Prev, 13,4393-402.
  16. Giftson JS, Jayanthi S, Nalini N (2010). Chemopreventive efficacy of gallic acid, an antioxidant and anticarcinogenic polyphenol, against 1, 2-dimethyl hydrazine induced rat colon carcinogenesis. Invest New Drugs, 28, 251-9.
  17. Goh KL, Quek KF, Yeo GT, et al (2005). Colorectal cancer in Asians: a demographic and anatomic survey in Malaysian patients undergoing colonoscopy. Aliment Pharmacol Ther, 22, 859-64.
  18. Habig WH, Pabst MJ, Jakoby WB (1974). Glutathione S-transferase. The first enzymatic step in mercapturic acid formation. J Biol Chem, 249, 7130-9.
  19. Janssen AM, Bosman CB, Kruidenier L, et al (1999). Superoxide dismutases in the human colorectal cancer sequence. J Cancer Res Clin Oncol, 125, 327-35.
  20. Janssen AM, Bosman CB, Kruidenier L, et al (1999). Superoxide dismutases in the human colorectal cancer sequence. J Cancer Res Clin Oncol, 125, 327-35.
  21. Jia XD, Han C (2000). Chemoprevention of tea on colorectal cancer induced by dimethylhydrazine in Wistar rats. World J Gastroenterol, 6, 699-703.
  22. Kamaleeswari M, Deeptha K, Sengottuvelan M, Nalini N (2006). Effect of dietary caraway (Carum carvi L.) on aberrant crypt foci development, fecal steroids, and intestinal alkaline phosphatase activities in 1,2-dimethylhydrazine-induced colon carcinogenesis. Toxicol Appl Pharmacol, 214, 290-6.
  23. Kanna PS, Mahendrakumar CB, Chakraborty T, et al (2003). Effect of vanadium on colonic aberrant crypt foci induced in rats by 1, 2 dimethyl hydrazine. World J Gastroenterol, 9, 1020-7.
  24. Le Leu RK, Brown IL, Hu Y, et al (2007). Effect of dietary resistant starch and protein on colonic fermentation and intestinal tumourigenesis in rats. Carcinogenesis, 28,240-5.
  25. Kelman Z, Zuo S, Arroyo MP, et al (1999). The C-terminal region of Schizosaccaromyces pombe proliferating cell nuclear antigen is essential for DNA polymerase activity. Proc Natl Acad Sci USA, 96, 9515-20.
  26. Khan R, Khan AQ, Lateef A, et al (2013). Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats. PLoS One, 8, 56020.
  27. Khare CP (2007). Indian Medicinal Plants. An Illustrated Dictionary. Springer, New York, p- 45.
  28. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951). Protein measurements with the folin phenol reagent. J Biol Chem, 193, 265-75.
  29. Malik R, Kamath N (2011). Anorectal mucinous adenocarcinoma in child: a case report. Eur J Pediatr, 170, 1461-3.
  30. Murakami A, Ohigashi H, Koshimizu K (1996). Anti-tumor promotion with food phytochemicals: a strategy for cancer chemoprevention. Biosci Biotechnol Biochem, 60, 1-8.
  31. Nagendraprabhu P, Sudhandiran G (2011). 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. Invest New Drugs, 29, 207-24.
  32. Nandhakumar R, Salini K, Niranjali Devaraj S (2012). Morin augments anticarcinogenic and antiproliferative efficacy against 7,12-dimethylbenz(a)-anthracene induced experimental mammary carcinogenesis. Mol Cell Biochem, 364, 79-92.
  33. Perse M, Cerar A (2011). Morphological and molecular alterations in 1,2 dimethylhydrazine and azoxymethane induced colon carcinogenesis in rats. J Biomed Biotechnol, 2011, 473964
  34. Niehius WG Jr, Samuelsson B (1968). Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem, 6, 126-30.
  35. Ohno K, Narushima S, Takeuchi S, et al (2001). Effect of bacterial metabolism in the intestine on colorectal tumors induced by 1,2-dimethylhydrazine in transgenic mice harboring human prototype C-Ha- ras genes. J Exp Clin Cancer Res, 20, 51-6.
  36. Pandurangan AK (2013). Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev, 14, 2201-5.
  37. Ramakrishnan G, Elinos-Baez CM, Jagan S, et al (2008). Silymarin down regulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma. Mol Cell Biochem, 313, 53-61.
  38. Reddy BS, Weisburger JH, Wynder EL (1974). Effects of dietary fat level and dimethylhydrazine on fecal acid and neutral sterol excretion and colon carcinogenesis in rats. J Natl Cancer Inst, 52, 507-11.
  39. Roncucci L, Medline A, Bruce WR (1991). Classification of aberrant crypt foci and microadenomas in human colon. Cancer Epidemiol Biomarkers Prev, 1, 57-60.
  40. Rotruck JT, Pope AL, Ganther HE, et al (1973). Selenium: Biochemical role as a component of glutathione peroxidase. Science, 179, 588-90.
  41. Salim EI, Abou-Shafey AE, Masoud AA, Elgendy SA (2011). Cancer chemopreventive potential of t-- Egyptian flaxseed oil in a rat colon carcinogenesis bioassayimplications for its mechanism of action. Asian Pac J Cancer Prev, 12, 2385-92.
  42. Stephanou G, Vlastos D, Vlachodimitropolus D, Demopolus NA (1996). A comparative study on the effect of MNU on human lymphocyte cultures in vitro evaluated by 06- mdG formation, micronuclei and sister chromatid exchanges induction. Cancer Lett, 109, 109-14.
  43. Sengupta A, Ghosh S, Das S (2004). Modulatory influence of garlic and tomato on cyclooxygenase-2 activity, cell proliferation and apoptosis during azoxymethane induced colon carcinogenesis in rat. Cancer Lett, 208, 127-36.
  44. Shpitz B, Hay K, Medline A, et al (1996). Natural history of aberrant crypt foci. A surgical approach. Dis Colon Rectum, 39, 763-7.
  45. Sreedharan V, Venkatachalam KK, Namasivayam N (2009). Effect of morin on tissue lipid peroxidation and antioxidant status in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis. Invest New Drugs, 27, 21-30.
  46. Sun M, Estrov Z, Ji Y, et al (2008). Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells. Mol Cancer Ther, 7, 464-73.
  47. Takahashi M, Minamoto T, Yamashita N, et al (1993). Reduction in formation and growth of 1,2-dimethylhydrazine-induced aberrant crypt foci in rat colon by docosahexaenoic acid. Cancer Res, 53, 2786-9.
  48. TakayamaT, Katsuki S, Takahashi Y, et al (1998). Aberrant crypt foci of the colon as precursors of adenoma and cancer. N Engl J Med, 339, 1277-84.
  49. Vargas PA, Alberts DS (1992). Primary prevention of colorectal cancer through dietary modification. Cancer, 70, 1229-35.<1229::AID-CNCR2820701507>3.0.CO;2-#
  50. Venkatachalam K, Gunasekaran S, Jesudoss VA, Namasivayam N (2013). The effect of rosmarinic acid on 1,2-dimethylhydrazine induced colon carcinogenesis. Exp Toxicol Pathol, 65, 409-18.
  51. Wargovich MJ, Chen CD, Harris C, Yang E, Velasco M (1995). Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and differentiation agents in the rat colon. Int J Cancer, 60, 515-9.
  52. Warrier PK, Nambiar VPK, Ramankutty C (1994). Indian medicinal plants, a compendium of 500 species. Vol I, Orient Longman Publisher, Chennai. pp 132-6.
  53. Weisburger JH( 1971). Colon carcinogens: their metabolism and mode of action. Cancer, 28, 60-70.<60::AID-CNCR2820280113>3.0.CO;2-U
  54. Yu BP (1994). Cellular defenses against damage from reactive oxygen species. Physiol Rev, 74, 139-62.
  55. Yusof AS, Isa ZM, Shah SA (2012). Dietary patterns and risk of colorectal cancer: a systematic review of cohort studies (2000-2011). Asian Pac J Cancer Prev, 13, 4713-7.

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