DOI QR코드

DOI QR Code

Ferutinin, an Apoptosis Inducing Terpenoid from Ferula ovina

  • Matin, Maryam Moghaddam (Department of Biology, Faculty of Science, Ferdowsi University of Mashhad) ;
  • Nakhaeizadeh, Hossein (Department of Biology, Faculty of Science, Ferdowsi University of Mashhad) ;
  • Bahrami, Ahamd Reza (Department of Biology, Faculty of Science, Ferdowsi University of Mashhad) ;
  • Iranshahi, Mehrdad (Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences) ;
  • Arghiani, Nahid (Department of Biology, Faculty of Science, Ferdowsi University of Mashhad) ;
  • Rassouli, Fatemeh Behnam (Department of Biology, Faculty of Science, Ferdowsi University of Mashhad)
  • Published : 2014.03.01

Abstract

A current hurdle in cancer management is the intrinsic or acquired resistance of cancer cells to chemical agents that restricts the efficacy of therapeutic strategies. Accordingly, there is an increasing desire to discover new natural compounds with selective toxicity to combat malignancies. In present study, the cytotoxic and apoptosis-inducing activities of ferutinin, a terpenoid derivative from Ferula ovina, were investigated on human breast (MCF7) and bladder (TCC) cancer cells as well as normal fibroblasts (HFF3).The toxicity and DNA damage inducing effects of ferutinin were studied by MTT and comet assays, DAPI and PI staining and DNA laddering. The $IC_{50}$ values of ferutinin were identified and compared with routine prescribed drugs, doxorubicin and vincristine, by MTT test. Alkaline comet assay and DAPI staining revealed DNA damage due to ferutinin, which was significantly (p<0.001) higher in MCF7 and TCC than HFF3 cells. Apoptosis induction was evidenced by PI staining and DNA laddering. Our results suggest that ferutinin could be considered as an effective anticancer agent for future in vivo and clinical experiments.

References

  1. Zargari A (1988). Medicinal Plants. Tehran, Iran: Tehran University Press.
  2. Shi W, Gould MN (2002). Induction of cytostasis in mammary carcinoma cells treated with the anticancer agent perillyl alcohol. Carcinogenesis, 23, 131-42. https://doi.org/10.1093/carcin/23.1.131
  3. Strong K, Mathers C, Epping-Jordan J, et al (2008). Preventing cancer through tobacco and infection control: How many lives can we save in the next 10 years? Eur J Cancer Prev, 17, 153-61. https://doi.org/10.1097/CEJ.0b013e3282b6fda8
  4. Zamaraeval MV, Hagelgansl AI, Abramovl AY, et al (1997). lonophoretic properties of ferutinin. Cell Calcium, 22, 235-41. https://doi.org/10.1016/S0143-4160(97)90062-2
  5. Peana AT, D'Aquila PS, Panin F, et al (2002). Antiinflammatory activity of linalool and linalyl acetate constituents of essential oils. Phytomedicine, 9, 721-6. https://doi.org/10.1078/094471102321621322
  6. Mansoor TA, Ramalho RM, Mulhovo S, et al (2009). Induction of apoptosis in HuH-7 cancer cells by monoterpene and b-carboline indole alkaloids isolated from the leaves of Tabernaemontana elegans. Bioorg Med Chem Lett, 19, 4255-8. https://doi.org/10.1016/j.bmcl.2009.05.104
  7. Mollazadeh S, Matin MM, Iranshahi M, et al (2010). The enhancement of vincristine cytotoxicity by combination with feselol. J Asian Nat Prod Res, 12, 569-75. https://doi.org/10.1080/10286020.2010.485565
  8. Mozaffarian V (1996). A Dictionary of Iranian Plant Names. Tehran, Iran: Farhang-e Moaser.
  9. Rassouli FB, Matin MM, Iranshahi M, et al (2009). Mogoltacin enhances the cytotoxicity of vincristine on TCC cell line. Phytomedicine, 16, 181-7. https://doi.org/10.1016/j.phymed.2008.06.011
  10. Rassouli FB, Matin MM, Iranshahi M, et al (2011a). Investigating the enhancement of cisplatin cytotoxicity on 5637 cells by combination with mogoltacin. Toxicol Vitro, 25, 469-74. https://doi.org/10.1016/j.tiv.2010.11.015
  11. Rassouli FB, Matin MM, Iranshahi M, et al (2011b). Investigating the cytotoxic and apoptosis inducing effects of monoterpenoid stylosin in vitro. Fitoterapia, 82, 742-9. https://doi.org/10.1016/j.fitote.2011.03.005
  12. Rivera E, Gomez H (2010). Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. Breast Cancer Res, 12, 2.
  13. Saddiq AA, Khayyat SA (2010). Chemical and antimicrobial studies of monoterpene: Citral. Pest Biochem Physiol, 98, 89-93. https://doi.org/10.1016/j.pestbp.2010.05.004
  14. Sahebkar A, Iranshahi M (2011). Volatile constituents of the genus Ferula (Apiaceae): a review. J Essent Oil Bear Pl, 14, 504-31. https://doi.org/10.1080/0972060X.2011.10643969
  15. Shang-Gao L, Zhen W, Jing L, et al (2012). Cytotoxic sesquiterpene lactones from Vernonia bockiana. Chinese J Nat Med, 10, 230-3. https://doi.org/10.3724/SP.J.1009.2012.00230
  16. Kanokmedhakul S, Lekphroma R, Kanokmedhakul K, et al (2012). Cytotoxic sesquiterpenes from luminescent mushroom Neonothopanus nimbi. Tetrahedron, 68, 8261-6. https://doi.org/10.1016/j.tet.2012.07.057
  17. Iranshahi M, Ghiadi M, Sahebkar A, et al (2009). Badrakemonin, a new eremophilane-type sesquiterpene from the roots of Ferula badrakema Kos.-Pol. Iran J Pharm Res, 8, 275-9.
  18. Iranshahi M, Sahebkar A, Hosseini ST, et al (2010). Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro and in vivo. Phytomedicine, 17, 269-73. https://doi.org/10.1016/j.phymed.2009.05.020
  19. Jagetia GC, Baliga MS, Venkatesh P, et al (2005). Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in vitro and in tumor-bearing mice. J Pharm Pharmacol, 57, 1213-9. https://doi.org/10.1211/jpp.57.9.0017
  20. Karimi G, Iranshahi M, Hosseinalizadeh F, et al (2010). Screening of acetylcholinesterase inhibitory activity of terpenoid and coumarin derivatives from the genus Ferula. Pharmacology Online, 1, 566-74.
  21. Koch E, Klaas CA, Rungeler P, et al (2001). Inhibition of inflammatory cytokine production and lymphocyte proliferation by structurally different sesquiterpene lactones correlates with their effect on activation of NF-kappaB. Biochem Pharmacol, 62, 795-801. https://doi.org/10.1016/S0006-2952(01)00714-6
  22. Kolli EH, Leon F, Benayache F, et al (2012). Cytotoxic sesquiterpene lactones and other constituents of Centaurea omphalotricha. J Braz Chem Soc, 23, 977-83. https://doi.org/10.1590/S0103-50532012000500026
  23. Lhuillier A, Fabre N, Cheble E, et al (2005). Daucane sesquiterpenes from Ferula hermonis. J Nat Prod, 68, 468-71. https://doi.org/10.1021/np049652h
  24. Macho A, Blanco-Molina M, Spagliardi P, et al (2004). Calcium ionophoretic and apoptotic effects of ferutinin in the human Jurkat T-cell line. Biochem Pharmacol, 68, 875-83. https://doi.org/10.1016/j.bcp.2004.05.016
  25. Geroushi A, Auzi AA, Elhwuegi AS, et al (2011). Antiinflammatory sesquiterpenes from the root oil of Ferula hermonis. Phytother Res, 25, 774-7. https://doi.org/10.1002/ptr.3324
  26. Do Socorro S, Rosa Mdo S, Mendonca-Filho RR, et al (2003). Antileishmanial activity of a linalool-rich essential oil from Croton cajucara. Antimicrob Agents Chemother, 47, 1895-901. https://doi.org/10.1128/AAC.47.6.1895-1901.2003
  27. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  28. Ferretti M, Bertoni L, Cavani F, et al (2012). Structural and histomorphometric evaluations of ferutinin effects on the uterus of ovariectomized rats during osteoporosis treatment. Life Sci, 90, 161-8. https://doi.org/10.1016/j.lfs.2011.11.001
  29. Greige-Gergesa H, Diabb Y, Faraha J, et al (2008). Ferutinin stability in human plasma and interaction with human serum albumin. Biopharm Drug Dispos, 29, 83-9. https://doi.org/10.1002/bdd.589
  30. Gurib-Fakim A (2006). Medicinal plants: traditions of yesterday and drugs of tomorrow. Mol Aspects Med, 27, 1-93. https://doi.org/10.1016/j.mam.2005.07.008
  31. Ibrahim NK, Buzdar AU, Asmar L, et al (2000). Doxorubicinbased adjuvant chemotherapy in elderly breast cancer patients: the M.D. Anderson experience with long term follow-up. Ann Oncol, 11, 1597-601. https://doi.org/10.1023/A:1008315312795
  32. Ikeda K, Arao Y, Otsuka H, et al (2002) Terpenoids found in the umbelliferae family act as agonists/antagonists for ERa and ERb: differential transcription activity between ferutininliganded ERa and ERb. Biochem Biophys Res Commun, 291, 354-60. https://doi.org/10.1006/bbrc.2002.6446
  33. Iranshahi M, Arfa P, Ramezani M, et al (2007). Sesquiterpene coumarins from Ferula szowitsiana and in vitro antileishmanial activity of 7-prenyloxycoumarins against promastigotes. Phytochemistry, 68, 554-61. https://doi.org/10.1016/j.phytochem.2006.11.002
  34. Iranshahi M, Kalategi F, Rezaee R, et al (2008). Cancer chemopreventive activity of terpenoid coumarins from Ferula species. Planta Med, 74, 147-50. https://doi.org/10.1055/s-2008-1034293
  35. Chiang LC, Ng LT, Cheng PW, et al (2005). Antiviral activities of extracts and selected pure constituents of Ocimum basilicum. Clin Exp Pharmacol Physiol, 32, 811-6. https://doi.org/10.1111/j.1440-1681.2005.04270.x
  36. Barrero AF, Oltra UE, Alvarez M, et al (2000). New sources and antifungal activity of sesquiterpene lactones. Fitoterapia, 71, 60-4. https://doi.org/10.1016/S0367-326X(99)00122-7
  37. Bocca C, Gabriel L, Bozzo F, et al (2004). A sesquiterpene lactone, costunolide, interacts with microtubule protein and inhibits the growth of MCF-7 cells. Chem Biol Interact, 147, 79-86. https://doi.org/10.1016/j.cbi.2003.10.008
  38. Chen CN, Huang HH, Wu CL, et al (2007). Isocostunolide, a sesquiterpene lactone, induces mitochondrial membrane depolarization and caspase-dependent apoptosis in human melanoma cells. Cancer Lett, 246, 237-52. https://doi.org/10.1016/j.canlet.2006.03.004
  39. Choi JH, Lee KT (2009). Costunolide-induced apoptosis in human leukemia cells: Involvement of c-Jun N-terminal kinase activation. Biol Pharm Bull, 32, 1803-8. https://doi.org/10.1248/bpb.32.1803
  40. Choi YK, Seo HS, Choi HS, et al (2012). Induction of Fasmediated extrinsic apoptosis, p21WAF1-related G2/M cell cycle arrest and ROS generation by costunolide in estrogen receptor-negative breast cancer cells, MDA-MB-231. Mol Cell Biochem, 363, 119-28. https://doi.org/10.1007/s11010-011-1164-z
  41. Crowell PL, Siar Ayoubi A, Burke YD (1996). Antitumorigenic effects of limonene and perillyl alcohol against pancreatic and breast cancer. Adv Exp Med Biol, 401, 131-6. https://doi.org/10.1007/978-1-4613-0399-2_10
  42. Crompton M (1999). The mitochondrial permeability transition pore and its role in cell death. Biochem J, 341, 233-49. https://doi.org/10.1042/0264-6021:3410233
  43. Dall'Acqua S, Maggi F, Minesso P, et al (2010). Identification of non-alkaloid acetylcholinesterase inhibitors from Ferulago campestris (Besser) Grecescu (Apiaceae). Fitoterapia, 81, 1208-12. https://doi.org/10.1016/j.fitote.2010.08.003
  44. Abd El-Razek MH, Ohta S, Hirata T (2003). Terpenoid coumarins of the genus Ferula. Heterocycles, 60, 689-716. https://doi.org/10.3987/REV-02-561
  45. Abourashed EA, Galal AM, Shibl AM (2011). Antimycobacterial activity of ferutinin alone and in combination with antitubercular drugs against a rapidly growing surrogate of Mycobacterium tuberculosis. Nat Prod Res, 25, 1142-9. https://doi.org/10.1080/14786419.2010.481623
  46. Abramov AY, Zamaraeva MV, Hagelgans AI, et al (2001). Infuence of plant terpenoids on the permeability of mitochondria and lipid bilayers. Biochim Biophys Acta, 1512, 98-110. https://doi.org/10.1016/S0005-2736(01)00307-8
  47. Abramov AY, Duchen MR (2003). Actions of ionomycin, 4-BrA23187 and a novel electrogenic $Ca^{2+}$ ionophore on mitochondria in intact cells. Cell Calcium, 33, 101-12. https://doi.org/10.1016/S0143-4160(02)00203-8
  48. Al-Mughrabi K, Aburjai TA (2003). Fungitoxic activity of root extracts from Ferula harmonis. Phytopathol Mediterr, 42, 141-8.
  49. Amin R, Kucuk O, Khuri FR, et al (2009). Perspectives for cancer prevention with natural compounds. J Clin Oncol, 27, 2712-25. https://doi.org/10.1200/JCO.2008.20.6235
  50. Bardon S, Picard K, Martel P (1998). Monoterpenes inhibit cell growth, cell cycle progression, and cyclin D1 gene expression in human breast cancer cell lines. Nutr Cancer, 32, 1-7. https://doi.org/10.1080/01635589809514708

Cited by

  1. 20(S)-Protopanaxadiol Induces Human Breast Cancer MCF-7 Apoptosis through a Caspase-Mediated Pathway vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7919