Anti-tumor and Chemoprotective Effect of Bauhinia tomentosa by Regulating Growth Factors and Inflammatory Mediators

  • Kannan, Narayanan (Department of Biotechnology, Karunya University) ;
  • Sakthivel, Kunnathur Murugesan (Department of Biotechnology, Karunya University) ;
  • Guruvayoorappan, Chandrasekaran (Department of Biotechnology, Karunya University)
  • Published : 2016.01.11


Cancer is a leading cause of death worldwide. Due to the toxic side effects of the commonly used chemotherapeutic drug cyclophosphamide (CTX), the use of herbal medicines with fewer side effects but having potential use as inducing anti-cancer outcomes in situ has become increasingly popular. The present study sought to investigate the effects of a methanolic extract of Bauhinia tomentosa against Dalton's ascites lymphoma (DAL) induced ascites as well as solid tumors in BALB/c mice. Specifically, B. tomentosa extract was administered intraperitonealy (IP) at 10 mg/kg. BW body weight starting just after tumor cell implantation and thereafter for 10 consecutive days. In the ascites tumor model hosts, administration of extract resulted in a 52% increase in the life span. In solid tumor models, co-administration of extract and CTX significantly reduced tumor volume (relative to in untreated hosts) by 73% compared to just by 52% when the extract alone was provided. Co-administration of the extract also mitigated CTX-induced toxicity, including decreases in WBC count, and in bone marrow cellularity and ${\alpha}$-esterase activity. Extract treatment also attenuated any increases in serum levels of $TNF{\alpha}$, iNOS, IL-$1{\beta}$, IL-6, GM-CSF, and VEGF seen in tumor-bearing hosts. This study confirmed that, the potent antitumor activity of B.tomentosa extract may be associated with immune modulatory effects by regulating anti-oxidants and cytokine levels.


Bauhinia tomentosa;anti-tumor activity;cyclophosphamide;Dalton's ascites lymphoma


  1. Aderogba MA, Mc Gaw LJ, Ogundaini AO, Eloff JN (2008). Cytotoxicity Study of antioxidant flavonoids from Bauhinia tomentosa leaf extract. Niger J Nat Prod medicine, 12, 50-4.
  2. Alenzi FQ, Bolkiny YS, Salem ML (2010). Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide. Br J Biomed Sci, 67, 20-8.
  3. Bancraft JD, Cook HC (1984). Manual of histological techniques. London: Churchill-Livingstone, 171-4.
  4. Blankenstein T, Qin Z (2003). The role of $IFN\gamma$ in tumor transplantation immunity and inhibition of chemical carcinogenesis. Curr Opin Immunol, 15, 148-54.
  5. Chen, JD, Xiong YQ, Dong K, et al (2014). Clinical significance of joint detection of serum VEGF, SIL-2R and HGF in patients with primary hepatocellular carcinoma before and after percutaneous microwave coagulation therapy. Asian Pac J Cancer Prev, 15, 4545-8.
  6. Cheng JC (2014). Transient knock down of grp78 reveals roles in serum ferritin mediated pro sin aammatory cytokine secretion in rat primary activated hepatic stellate cells. Asian Pac J Cancer Prev, 15, 605-10.
  7. Corti A, Franzini M, Paolicchi A, Pompella A (2010). $\gamma$-Glutamyl-transferase of cancer cells: At the crossroads of tumor progression, drug resistance, and drug targeting. Anticancer Res, 30, 1169-81.
  8. Deepak P, Kumar S, Acharya A (2008). Overexpression of IL-13 in a murine T-cell lymphoma: A possible factor of DL-induced immunosuppression and tumor progression. Cancer Invest, 27, 641-49.
  9. Devaki K, Beulah U, Akila G, Narmadha R, Gopalakrishnan VK (2011). Glucose lowering effect of aqueous extract of Bauhinia tomentosa on alloxan-induced Type 2 diabetes mellitus in Wistar rats. J Basic Clin Pharm, 2, 167-74.
  10. Diwanay S, Chitre D, Patwardhan B (2004). Immunoprotection by botanical drugs in cancer chemotherapy. J Ethnopharmacol, 90, 49-55.
  11. Dominici S, Valentini M, Maellaro E, et al (1999). Redox modulation of cell surface protein thiols in U937 lymphoma cells: the role of gamma-glutamyl transpeptidase-dependent $H_2O_2$ production and S-thiolation. Free Radic Biol Med, 27, 623-35.
  12. Goldberg JE, Schwertfeger KL (2010). Proinflammatory cytokines in breast cancer: mechanisms of action and potential targets for therapeutics. Curr Drug Targets, 11, 1133-46.
  13. Gopalakrishnan S, Vadivel E (2011). Antibacterial and antifungal activity of the bark of bauhinia tomentosa. Int J Pharm. Sci, 2, 104-9.
  14. Green LC, Wagner, DA, Glogowski J, et al (1982). Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem, 126, 131-8.
  15. Grivennikov SI, Greten FR, Karin M (2010). Immunity, inflammation, and cancer. Cell, 140, 883-99.
  16. Haque R, Parvez S, Pandey S (2003). Aqueous extract of walnut (juglans regia l.) protects mice against cyclophosphamide induced biochemical toxicity. Hum Exp Toxicol, 22, 473-80.
  17. Huang MT, Wood AW, Newmark HL (1984). Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by phenolic plant flavonoids. Carcinogenesis, 4, 1631-37.
  18. Jemal A, Siegel R, Ward, E, et al (2009). Cancer statistics 2009. CA Cancer J Clin, 59, 225-49.
  19. Kannan N, Guruvayoorappan C (2013). Protective effect of Bauhinia tomentosa on acetic acid induced ulcerative colitis by regulating antioxidant and inflammatory mediators. Int Immunopharmacol, 16, 57- 66.
  20. Kannan N, Renitta RE, Guruvayoorappan C (2010). Bauhinia tomentosa stimulates the immune system and scavenges free radical generation in vitro. J Basic Clin Physiol Pharmacol, 21, 157-68.
  21. Kiuchi H, Takao T, Yamamoto K, et le (2009). Sesquiterpene lactone parthenolide ameliorates bladder inflammation and bladder over-activity in cyclophosphamide-induced rat cystitis model by inhibiting NF-${\kappa}B$ phosphorylation. J Urol, 181, 2339-48.
  22. Kolb J P. (2000). Mechanisms involved in the pro- and antiapoptotic role of NO in human leukemia. Leukemia, 14, 1685-94.
  23. Lewis AM, Varghese S, Xu H, Alexander HR (2006). Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. J Transl Med, 4, 48.
  24. Majumdar UK, Gupta M, Maiti S (1997). Antitumour activity of hygrophila spinosa on Ehrlich ascites carcinoma and sarcoma-180 induced mice. Ind J exp biol, 35, 473-7.
  25. Malek TR (2003). The main function of IL-2 is to promote the development of T regulatory cells. J Leukoc Bio, 74, 961-5.
  26. Mannangatti V, Ayyasamy B, Rangasamy M, Natesan S (2010). Antioxidant potential of ethanolic extract of Bauhinia tomentosa (Linn) flower. Res J Pharma BioChem Sci, 1, 143-7.
  27. Manusama ER, Stavast J, Durante NM, Marquet RL, Eggermont AM (1996). Isolated limb perfusion with TNF alpha and melphalan in a rat osteosarcoma model: a new anti-tumour approach. Eur J Surg Oncol, 22, 152-7.
  28. Moron MS, Depierre JW, Mannervik B (1979). Levels of glutathione, glutathione reductase and glutathione-Stransferase activities in rat lung and liver. Biochim Biophys Acta, 582, 67-78.
  29. Murata M, Suzuki T, Midorikawa K (2004). Oxidative DNA damage by a hydroperoxide derivative of cyclophosphamide. Free Radic Biol Med, 37, 793-802.
  30. Natesan S, Badami S, Dongre SH, Godavarthi A (2007). Antitumor activity and antioxidant status of the methanol extract of Careya arborea bark against Dalton's lymphoma ascites-induced ascitic and solid tumor in mice. J Pharmacol Sci. 103, 12-23.
  31. Newman DJ, Cragg GM (2012). Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod, 75, 311-35.
  32. Ouyang GF, Saio M, Suwa T, et al (2006). Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro. Int J Oncol, 28, 1201-8.
  33. Preethi KC, Siveen KS, Kuttan R, Kuttan G (2010). Inhibition of metastasis of B16F-10 melanoma cells in C57BL/6 mice by an extract of Calendula officinalis L flowers. Asian Pac J Cancer Prev, 11, 1773-9.
  34. Rajkapoor B, Jayakar B, Murugesh N, Sakthisekaran D (2006). Chemoprevention and cytotoxic effect of Bauhinia variegata against N-nitrosodiethylamine induced liver tumors and human cancer cell lines. J Ethnopharmacol, 104, 407-9.
  35. Rates SMK (2001). Plants as source of drugs. Toxicon. 39, 603-13.
  36. Richard JS, Annet H, David KS, Jacquetine MM, Larry, DW (1997). Interleukin-6 structure-function relationship. Prot sci, 6, 929-55.
  37. Ruttimann J (2007). Macrophages and nitric oxide: A deadly combination. J Exp Med, 204, 3057.
  38. Sakthivel KM, Guruvayoorappan C (2012). Biophytum sensitivum: Ancient medicine, modern targets. J Adv Pharm Technol Res, 3, 83-91.
  39. Sakthivel KM, Kannan N, Angeline A, et al (2012). Anticancer activity of acacia nilotica (l.) wild. ex. delile subsp. indica against dalton's ascitic lymphoma induced solid and ascitic tumor Model. Asian Pac J Cancer Prev, 13, 3989-95.
  40. Sakthivel KM, Guruvayoorappan C (2013). Acacia ferruginea inhibits tumor progression by regulating inflammatory mediators $TNF{\alpha}$, iNOS, COX-2, IL-$1\beta$, IL-6, $IFN\gamma$, IL-2, GM-CSF, and pro-angiogenic growth factor VEGF. Asian Pac J Cancer Prev, 6, 3909-19.
  41. Siest G, Courtay C, Oster T, et al (1992). Gammaglutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gammaglutamyltransferase polypeptide in human tissue. Biochem Pharmacol, 43, 2527-33.
  42. Slingluff CL, Gina R, Petroni GV, et al (2003). Clinical and immunologic results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol, 21, 4016-26.
  43. Small E J, Sacks N, Nemunaitis J, et al (2007). Granulocyte macrophage colony-stimulating factor-secreting allogeneic cellular immuno-therapy for hormone-refractory prostate cancer. Clin Cancer Res, 13, 3883-91.
  44. Soiffer R, Hodi FS, Haluska F, et al (1998). Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci, 95, 13141-46.
  45. Strasak AM, Rapp K, Brant LJ, et al (2008). The vorarlberg health monitoring and promotion program study group: association of $\gamma$-glutamyl-transferase and risk of cancer incidence in men: a prospective study. Cancer Res, 68, 3970-7.
  46. Tenhagen TL, Van der Veen AH, Nooijen PT, et al (2000). Low-dose TNF-$\alpha$ augments anti-tumor activity of stealth liposomal doxorubicin (DOXIL) in soft tissue sarcomabearing rats. Int J Cancer, 87, 829-37.<829::AID-IJC12>3.0.CO;2-C
  47. Trachootham D, Alexandre J, Huang P (2009). Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat Rev Drug Discov, 8, 579-91.
  48. Verheul HM, Pinedo HM (2000). The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and early clinical development of VEGF-receptor kinase inhibitors. Clin Breast Cancer, 1, 80-4.
  49. Zarei S, Schwenter F, Luy P, et al (2009). Role of GM-CSF signaling in cell-based tumor immunization. Blood, 25, 6658-68.

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