Anti-proliferative and Apoptotic Effects of Basella rubra (L.) Against 1, 2-Dimethyl Hydrazine-induced Colon Carcinogenesis in Rats

  • Kilari, Bhanu Priya (Department of Biotechnology, Sri Padmavathi Mahila University) ;
  • Kotakadi, Venkata Subbaiah (DST-PURSE Centre, Sri Venkateswara University) ;
  • Penchalaneni, Josthna (Department of Biotechnology, Sri Padmavathi Mahila University)
  • Published : 2016.02.05


Colorectal cancer is a very prevalent diagnosed cancer. The current study was performed in order to examine the role of BRAE (Basella rubra aqueous extract) in regulating aberrant crypt foci (ACF) formation, cell proliferation and inhibition of apoptosis in a colon carcinogenesis model in male Wistar rats. Rats were randomly allocated into six groups. Group I served as control, and group II acted as a drug control administered BRAE (250mg/kg b.w.) orally for 30 weeks. Rats in group III-VI were given subcutaneous injections of DMH (25mg/kg b.w. weekly) for 15 weeks to initiate colon carcinogenesis. Those in group IV and VI were administered BRAE along with DMH injections. Rats in group V were administered with BRAE after cessation of DMH injection. After 30 weeks of experimental period colons were obtained from experimental groups and analyzed for ACF incidence, argyrophilic nucleolar organizing region-associated proteins (AgNOR) count, histopathological and immunohistochemical changes. Only in DMH exposed groups were ACF and AgNOR numbers increased. Administration of BRAE appreciably decreased the numbers of ACF and AgNOR in BRAE treated groups. Histopathological findings revealed a high level of dysplastic changes with decreased number of goblet cells found only in only DMH injected rats. Administration of BRAE in treated group rats reversed these changes. Expression markers for cell proliferation (PCNA and Ki67) were elevated in DMH treated rats, but reduced with BRAE treatement. This expression was reversed with apoptosis markers (p53 and Caspase-3). Thus the results results of the present study were found to be significant and confirmed the potential efficacy of BRAE against colon carcinogenesis.


Basella rubra;1, 2-dimethylhydrazine (DMH);colon cancer;expression markers


  1. Abdelkader B, Djerdjouri B, Laroche-Clary A, et al (2012). Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-1 and HES-1 transcripts in 1, 2-dimethylhydrazine-colon carcinogenesis in mice. Toxicol, 302, 308-17.
  2. Adhikari R, Naveen Kumar HN, Shruthi SD (2012). A review on medicinal importance of Basella alba L. Int J Pharm Sci Drug Res, 4, 110-14.
  3. Alrawi SJ, Schiff M, Carroll RE, et al (2006). Aberrant crypt foci. Anticancer Res, 26,107-9.
  4. Ameilinda M, Farida S, Putri LW, et al (2011). Antiproliferative activity of ethanolic extract of Ciplukan herbs (Physalis angulata L.) on 7, 12-Dimethylbenz[a]nthracene-induced rat mammary carcinogenesis. Indonesian J Cancer Chemoprevent, 2, 227-32.
  5. Bird RP (1987). Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: Preliminary findings. Cancer Lett, 2, 147-51.
  6. Colorectal Cancer Facts & Figures 2014-2016 (2014).
  7. Das D, Arber N, Jankowski JA (2007). Chemoprevention of colorectal cancer. Digest, 76, 51-67.
  8. de Moura NA, Caetano BFR, Sivieri K, et al (2012). Protective effects of yacon (Smallanthus sonchifolius) intake on experimental colon carcinogenesis. Food Chem Toxicol, 50, 2902-10.
  9. Dong C-A, Hayashi K, Mizukoshi Y, et al (2012). Structures and anti-HSV-2 activities of neutral polysaccharides from an edible plant, Basella rubra L. Intl J Biol Macromol, 50, 245-9.
  10. Guizani N, Ibrahim Waly M, Rahman MS (2013). Nabag (Zizyphus spina-christi) extract prevents aberrant crypt foci development in colons of azoxymethane-treated rats by abrogating oxidative stress and inducing apoptosis. Asian Pac J Cancer Prev, 14, 5031-35.
  11. Gellad ZF, Provenzale D (2010). Colorectal cancer: National and international perspective on the burden of disease and public health impact. Gastroenterol, 138, 2177-90.
  12. Haenszel W, Correa P (1973). Cancer of the large intestine. Epidemiological findings. Dis Colon Rectum, 16, 371-77.
  13. Halliwell B (2007). Dietary polyphenols: good, bad, or indifferent for your health? Cardiovasc Res, 73, 341-7.
  14. Hamiza OO, Muneeb U Rehman, Mir Tahir, 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.
  15. Jin Y, Kotakadi VS, Ying L, et al (2008). American ginseng suppresses inflammation and DNA damage associated with mouse colitis. Carcinogenesis, 29, 2351-9.
  16. Katarzyna P, Bennett RN, Kromer K, et al (2007). Assessment of the antiproliferative activity of carrot and apple extracts, Pol J Food Nutr Sci, 57, 307-14.
  17. Katsuki T, Hirata K, Ishikawa H, et al (2006). Aged garlic extract has chemopreventative effects on 1, 2-dimethylhydrazine-induced colon tumors in rats. J Nutr, 136, 847-51.
  18. Khan R, Khan AQ, Qamar W, et al (2012). Chrysin protects against cisplatin-induced colon toxicity via amelioration of oxidative stress and apoptosis: probable role of p38 MAPK and p53. Toxicol Appl Pharmacol, 258, 315-29.
  19. Kim Y-N (1999). Folate and carcinogenesis: Evidence, mechanisms, and implications. J Nutr Biochem, 10, 66-88.
  20. Kotakadi VS, Jin Y, Hofseth AB, et al (2008). Ginkgo biloba extract EGb 761 has anti-inflammatory properties and ameliorates colitis in mice by driving effector T cell apoptosis. Carcinogenesis, 29, 1799-1806.
  21. Kupcinskas J, Gyvyte U, Bruzaite I, et al (2014). Common genetic variants of PSCA, MUC1 and PLCE1 genes are not associated with colorectal cancer. Asian Pac J Cancer Prev, 16, 6027-32.
  22. Lakshmi Prasuna CP, Chakradhar RPS, Rao JL, et al (2009). EPR and IR spectral investigations on some leafy vegetables of Indian origin. Spectrochim Acta Part A, 74, 140-7.
  23. Lofano K, Principi M, Scavo MP, et al (2012). Dietary lifestyle and colorectal cancer onset, recurrence and survival: myth or reality? J Gastrointest Cancer, 44, 1-11.
  24. Lund EK (2006). Dietary fatty acids and colon cancer. Scand J Food Nutr, 50, 39-44.
  25. McLellan EA, Medline A, Bird RP (1991). Sequential analyses of the growth and morphological characteristics of aberrant crypt foci: putative preneoplastic lesions. Cancer Res, 51,
  26. Murakami T, Hirano K, Yoshikawa M (2001). Medicinal foodstuffs. XXIII. Structures of new oleanane-type triterpene oligoglycosides, basellasaponins A, B, C, and D, from the fresh aerial parts of Basella rubra L. Chem Pharm Bull, 49, 776-9.
  27. Nagarajan A, Gomathi R, Manian S, et al (2012). Evaluation of Basella rubra l., rumex nepalensis spreng. and Commelina benghalensis L. for antioxidant activity. Int J Pharm Pharm Sci, 4, 714-20.
  28. 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, NF k-B and COX-2. Invest New Drugs, 29, 207-24.
  29. Perse M, Cerar A (2011). Morphological and molecular alterations in 1, 2 dimethylhydrazine and azoxymethane induced colon carcinogenesis in rats. J Biomed Biotechnol, 473964, 1-14.
  30. Porter AG, Janicke RU (1999). Emerging roles of caspase-3 in apoptosis. Cell Death Differ, 2, 99-104.
  31. Poomphakwaen K, Promthet S, Suwanrungruang K, et al (2015). Risk factors for colorectal cancer in Thailand. Asian Pac J Cancer Prev, 16, 6105-09.
  32. Priya K, Ankur Gupta, Surabhi Mahajan, et al (2015). Evaluation of antimicrobial properties of Basella rubra methanolic extracts on selected microorganisms. Int J Pharm Sci Res, 6, 334-6.
  33. Rodrigues MAM, Silva LAG, Salvadori DMF, et al (2002). Aberrant crypt foci and colon cancer: comparison between a short- and medium -term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats. Braz J Med Bio Res, 35, 351-5.
  34. Rosenberg DW, Liu Y (1995). Induction of aberrant crypts in murine colon with varying sensitivity to colon carcinogenesis. Cancer Lett, 92, 209-14.
  35. Sanganna B, Kulkarni AR (2013). Effect of Citrus reticulata essential oil on aberrant crypt foci (acf) development in1, 2-dimetylhydrazine induced colon carcinogenesis rats. Int J Pharmaceut Appl, 4, 29-37.
  36. Sengottuvelan M, Nalini N (2006). Dietary supplementation of resveratrol suppresses colonic tumour incidence in 1, 2-dimethylhydrazine-treated rats by modulating biotransforming enzymes and aberrant crypt foci development. Br J Nutr, 96, 145-53.
  37. Summart R, Chewonarin T (2014). Purple rice extract supplemented diet reduces DMH-induced aberrant crypt foci in the rat colon by inhibition of bacterial ${\beta}$-glucoronidase. Asian Pac J Cancer Prev, 15, 749-55.
  38. Tanaka T, Yasui Y, Tanaka M, et al (2009). Melatonin suppresses AOM/DSS-induced large bowel oncogenesis in rats. Chem Biol Interact, 177, 128-36.
  39. Tudek B, Bird RP, Bruce WR (1989). Foci of aberrant crypts in the colons of mice and rats exposed to carcinogens associated with foods. Cancer Res, 49, 1236-40.
  40. Van Duijnhoven FJ, Bueno-De-Mesquita HB, Ferrari P, et al (2009). Fruit, vegetables and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr, 89, 1441-52.
  41. Venkatachalam K, Gunasekaran S, Jesudoss VA, et al (2013). The effect of rosamarinic acid on 1, 2-dimethylhydrazine induced colon carcinogenesis. Exp Toxicol Pathol, 65, 409-18.
  42. Xu G, Ren G, Xu X, et al (2010). Combination of curcumin and green tea catechins prevents dimethylhydrazine- induced colon carcinogenesis. Food Chem Toxicol, 48, 390-5.

Cited by

  1. Expression of Pro- and Antiapoptotic Factors in Multinuclear Macrophages of BCG-Infected Mice In Vitro vol.165, pp.4, 2018,
  2. Identification and characterization of bioactive phenolic constituents, anti-proliferative, and anti-angiogenic activity of stem extracts of Basella alba and rubra vol.55, pp.5, 2018,