Ethanolic Extract from Derris scandens Benth Mediates Radiosensitzation via Two Distinct Modes of Cell Death in Human Colon Cancer HT-29 Cells

  • Hematulin, Arunee (Radiobiology Research Unit, Department of Radiation Technology, Faculty of Allied Health Sciences) ;
  • Ingkaninan, Kornkanok (Department of Pharmaceutical Chemistry and Pharmacognosy, Naresuan University) ;
  • Limpeanchob, Nanteetip (Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University) ;
  • Sagan, Daniel (Radiobiology Research Unit, Department of Radiation Technology, Faculty of Allied Health Sciences)
  • Published : 2014.02.28


Enhancing of radioresponsiveness of tumors by using radiosensitizers is a promising approach to increase the efficacy of radiation therapy. Recently, the ethanolic extract of the medicinal plant, Derris scandens Benth has been identified as a potent radiosensitizer of human colon cancer HT29 cells. However, cell death mechanisms underlying radiosensitization activity of D scandens extract have not been identified. Here, we show that treatment of HT-29 cells with D scandens extract in combination with gamma irradiation synergistically sensitizes HT-29 cells to cell lethality by apoptosis and mitotic catastrophe. Furthermore, the extract was found to decrease Erk1/2 activation. These findings suggest that D scandens extract mediates radiosensitization via at least two distinct modes of cell death and silences pro-survival signaling in HT-29 cells.


Radiosensitizer;Derris scandens benth;radiotherapy;apotosis mitotic catastrophe


  1. Sandur SK, Deorukhkar A, Pandey MK, Pabon AM, Shentu S, Guha S, et al (2009). Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int J Radiat Oncol Biol Phys, 75, 534-42.
  2. Schmitt CA (2003). Senescence, apoptosis and therapy--cutting the lifelines of cancer. Nat Rev Cancer, 3, 286-95.
  3. Slinker BK (1998) The statistics of synergism. J Mol Cell Cardiol, 30, 723-31.
  4. Vakifahmetoglu H, Olsson M and Zhivotovsky B (2008). Death through a tragedy: mitotic catastrophe. Cell Death Differ, 15, 1153-62.
  5. Verheij M, Vens C, Van Triest B (2010). Novel therapeutics in combination with radiotherapy to improve cancer treatment: rationale, mechanisms of action and clinical perspective. Drug Resist Updat, 13, 29-43.
  6. Verheij M (2008). Clinical biomarkers imaging for radiotherapyinduced cell death. Cancer Metastasis Rev, 27, 471-80.
  7. Vitale I, Galluzzi L, Castedo M, Kroemer G (2011). Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol, 12, 385-92.
  8. Tiangburanatham W (1996). Dictionary of Thai Medicinal Plants. Bangkok:Prachumtong Printing
  9. Weaver BA, Cleveland DW (2005). Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death. Cancer Cell, 8, 7-12.
  10. Wilson GD, Bentzen SM, Harari PM (2006). Biologic basis for combining drugs with radiation. Semin Radiat Oncol, 16, 2-9.
  11. Mirzayans R, Andrais B, Scott A, Tessier A, Murray D (2007) A sensitive assay for the evaluation of cytotoxicity and its pharmacologic modulation in human solid tumor-derived cell lines exposed to cancer-therapeutic agents. J Pharm Pharm Sci, 10, 298-311.
  12. Laupattarakasem P, Houghton PJ, Hoult JR (2004) Antiinflammatory isoflavonoids from the stems of Derris scandens. Planta Med, 70,496-501.
  13. Mannino M, Chalmers AJ (2011) Radioresistance of glioma stem cells: intrinsic characteristic or property of the 'microenvironment-stem cell unit. Mol Oncol, 5, 374-86.
  14. McGinn CJ, Lawrence TS (2001) Recent advances in the use of radiosensitizing nucleosides. Semin Radiat Oncol 11, 270-80.
  15. Moding EJ, Kastan MB, Kirsch DG (2013) Strategies for optimizing the response of cancer and normal tissues to radiation. Nat Rev Drug Discov, 12, 526-42
  16. Park OJ, Shin JI (2004) Proapoptotic potentials of genistein under growth stimulation by estrogen. Ann N Y Acad Sci, 1030, 410-18.
  17. Pisamai Laupattarakasem BS, Laupattarakasem W (2007). Antimigration of cancer cells by Derris scandens on cholangiocarcinoma cells. Srinagarind Med J, 22, 339-45.
  18. Rao SA, Srinivas PV, Tiwari AK, Vanka UM, Rao RV, et al (2007). Isolation, characterization and chemobiological quantification of alpha-glucosidase enzyme inhibitory and free radical scavenging constituents from Derris scandens Benth. J Chromatogr B Analyt Technol Biomed Life Sci, 855, 166-72.
  19. Rukachaisirikul V, Sukpondma Y, Jansakul C and Taylor WC (2002). Isoflavone glycosides from Derris scandens. Phytochemistry, 60, 827-34.
  20. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S (2004). Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem, 73, 39-85.
  21. Hematulin A IK, Limpeanchob N, Sagan D (2011) Derris scandens Benth extract radiosensitizes HT-29 colon cancer cells. Siriraj Med J, 63, 85-8.
  22. Hall EJ, Giaccia, Amato J (2006) Radiobiology for the radiologist. Philladelphia:Lippincott Williams & Wilkins
  23. Hara T, Omura-Minamisawa M, Kang Y, Cheng C, Inoue T (2008) Flavopiridol potentiates the cytotoxic effects of radiation in radioresistant tumor cells in which p53 is mutated or Bcl-2 is overexpressed. Int J Radiat Oncol Biol Phys, 71, 1485-95.
  24. Hanson PW, Elaimy AL, Lamoreaux WT, Demakas JJ, Fairbanks RK, et al (2012) A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases. World J Surg Oncol, 10, 176
  25. Hematulin A, Meethang S, Ingkaninan K, Sagan D (2012). Derris scandens Benth extract potentiates radioresistance of Hep-2 laryngeal cancer cells. Asian Pac J Cancer Prev, 13, 1289-95.
  26. Hematulin A, Sagan D, Eckardt-Schupp F, Moertl S (2008) NBS1 is required for IGF-1 induced cellular proliferation through the Ras/Raf/MEK/ERK cascade. Cell Signal, 20, 2276-85.
  27. Junttila MR, Li SP, Westermarck J (2008) Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J, 22, 954-65.
  28. Katz D, Ito E, Liu FF (2009) On the path to seeking novel radiosensitizers. Int J Radiat Oncol Biol Phys, 73, 988-96.
  29. Kim KC, Jun HJ, Kim JS, Kim IG (2008) Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells. Int J Mol Med, 21, 489-98.
  30. Kohno M, Tanimura S, Ozaki K (2011) Targeting the extracellular signal-regulated kinase pathway in cancer therapy. Biol Pharm Bull, 34, 1781-4..
  31. Chou TC, Matin N (2005) CompuSyn for Drug Combinations: PC Software and User's Guide: A Computer Program for Quantitation of Synergism and Antagonism in Drug Combinations, and the Determination of IC50 and ED50 and LD50 Values, Paramus, (NJ): ComboSyn Inc.
  32. Chendil D, Ranga RS, Meigooni D, Sathishkumar S and Ahmed MM (2004) Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene, 23, 1599-607.
  33. Chou TC (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev, 58, 621-81.
  34. Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul, 22, 27-55.
  35. Coventry BJ, Ashdown ML (2012). Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation. Cancer Manag Res, 4, 137-49.
  36. De Schutter H, Nuyts S (2009) Radiosensitizing potential of epigenetic anticancer drugs. Anticancer Agents Med Chem, 9, 99-108.
  37. Ewings KE, Wiggins CM, Cook SJ (2007) Bim and the prosurvival Bcl-2 proteins: opposites attract, ERK repels. Cell Cycle, 6, 2236-40.
  38. Gavriel H, McArthur G, Sizeland A, Henderson M (2011). Review: mucosal melanoma of the head and neck. Melanoma Res, 21, 257-66.
  39. Girdhani S, Bhosle SM, Thulsidas SA, Kumar A, Mishra KP (2005) Potential of radiosensitizing agents in cancer chemoradiotherapy. J Cancer Res Ther, 1, 129-31.
  40. Habr-Gama A, Perez RO, Sao Juliao GP, Proscurshim I, Gama- Rodrigues J (2011). The need for effective radiosentitizing agents: experience in patients with complete pathological response. Anticancer Drugs, 22, 308-10.
  41. Balcer-Kubiczek EK (2012). Apoptosis in radiation therapy: a double-edged sword. Exp Oncol, 34, 277-85.
  42. Cagnol S, Chambard JC (2010). ERK and cell death: mechanisms of ERK-induced cell death-apoptosis, autophagy and senescence. FEBS J, 277, 2-21.

Cited by

  1. Anti-Cancer Natural Products Inducing Cross-talk between Apoptosis and Autophagy Mutual Proteins to Regulate Cancer Cell Death: Design of Future Green Anticancer Therapies vol.16, pp.14, 2015,