Radiosensitization Effects of a Zataria multiflora Extract on Human Glioblastoma Cells

  • Aghamohammadi, Azar (Traditional and Complementary Medicine Research Center, Mazandaran University of Medical Sciences) ;
  • Hosseinimehr, Seyed Jalal (Traditional and Complementary Medicine Research Center, Mazandaran University of Medical Sciences) ;
  • Ghasemi, Arash (Department of Radiology and Radiation Oncology, Mazandaran University of Medical Sciences) ;
  • Azadbakht, Mohammad (Traditional and Complementary Medicine Research Center, Mazandaran University of Medical Sciences) ;
  • Pourfallah, Tayyeb Allahverdi (Department of Biochemistry and Biophysics, Faculty of Medicine, Mazandaran University of Medical Sciences)
  • Published : 2015.11.04


Background: Although radiotherapy is one of the most effective strategies in the treatment of cancers, it is associated with short and long term side effects on normal tissues. Zataria multiflora Boiss (Laminacea) (ZM) has several biological properties such as antioxidant and anti-inflammation activities.Here we investigated cell killing effects of a hydroalcoholic Zataria multiflora extract on cell death induced by ionizing radiation in a human glioblastoma cell line (A172) and human non-malignant fibroblasts (HFFF2) in vitro. Materials and Methods: A172 and HFFF2 cells were treated with a hydroalcoholic extract of dried aerial parts of Zataria multiflora at different concentrations (25, 50, 100, 150 and $200{\mu}g/ml$) and then exposed to ionizing radiation (IR). Cell proliferation and DNA fragmentation were evaluated. Thymol content in the extract was analyzed and quantified by HPLC methods. Results: A172 cell proliferation was significantly inhibited by ZM. The percentage cell survival was $91.8{\pm}8.57$ for cells treated with $200{\mu}g/ml$ of ZM extract alone while it was $76.0{\pm}4.27$ and $66.2{\pm}8.42$ for cells treated with ZM and exposed to IR at doses of 3Gy and 6Gy, respectively. Radiation-induced apoptosis in A172 cells was significantly increased following treatment with ZM at doses of $200{\mu}g/ml$. ZM extract did not exhibit any enhanced cell killing effects and apoptosis caused by IR on HFFF2 cells. Conclusions: These data show selective radiosensitization effects of ZM in A172 cells apparently due to increased radiation-induced apoptosis.


Ionizing radiation;Zataria multiflora;anti-proliferation;apoptosis;radiosensitive


  1. Alizadeh NS, Khoei EM, Fazelimanesh M, et al (2009). Antibacterial effects of Zataria multiflora boiss (shirazi avishan extract) on urinary tract escherichia coli infections. Res J Biological Sci, 4, 891-4.
  2. Amanlou M, Beitollahi JM, Abdollahzadeh S, et al (2006). Miconazole gel compared with Zataria multiflora Boiss. gel in the treatment of denture stomatitis. Phytother Res, 20, 966-9.
  3. Antoccia A, Sgura A, Berardinelli F, et al (2009). Cell cycle perturbations and genotoxic effects in human primary fibroblasts induced by low-energy protons and X/${\gamma}$-rays. J Radiat Res, 50, 457-68.
  4. Baskar R, Lee KA, Yeo R, et al (2012). Cancer and radiation therapy: current advances and future directions. Int J Med Sci, 9, 193-9.
  5. Chakravarti A, Palanichamy K (2008). Overcoming therapeutic resistance in malignant gliomas: current practices and future directions. Cancer Treat Res, 139, 173-89
  6. El-Sayed EM, Abd-Allah AR, Mansour AM, El-Arabey AA (2015). Thymol and carvacrol prevent cisplatininduced nephrotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol, 29, 165-72.
  7. Fang EF, Ng TB (2013). Antitumor potential and other emerging medicinal properties of natural compounds, springer.
  8. Hosseinimehr SJ, Mahmoudzadeh A, Ahmadi A, et al (2011). The radioprotective effect of Zataria multiflora against genotoxicity induced by ${\gamma}$ irradiation in human blood lymphocytes. Cancer Biother Radiopharm, 26, 325-9.
  9. Hosseinzadeh H, Ramezani M, Salmani G (2000). Antinociceptive, anti-inflammatory and acute toxicity effects of Zataria multiflora Boiss extracts in mice and rats. J Ethnopharmacol, 73, 379-85.
  10. Jaafari A, Mouse H, M’Bark L, et al (2009). Differential antitumor effect of essential oils and their major components of Thymus broussonettii: relationship to cell cycle and apoptosis induction. Herba Polonica, 55, 36-50.
  11. Jaffary F, Ghannadi A, Siahpoush A (2004). Antinociceptive effects of hydroalcoholic extract and essential oil of Zataria multiflora. Fitoterapia, 75, 217-20.
  12. Karkabounasli S, Metsios A, Lekkas P, et al (2006). Anticarcinogenic and antiplatelet effects of carvacrol. Expe Oncol, 28, 121-5.
  13. Kavoosi G, Teixeira da Silva JA, Saharkhiz MJ (2012). Inhibitory effects of Zataria multiflora essential oil and its main components on nitric oxide and hydrogen peroxide production in lipopolysaccharide-stimulated macrophages. J Pharm Pharmacol, 64, 1491-500.
  14. Kma L (2014). Plant extracts and plant-derived compounds: promising players in a countermeasure strategy against radiological exposure. Asian Pac J Cancer Prev, 15, 2405-25.
  15. Lachumy SJ, Oon CE, Deivanai S, et al (2013). Herbal remedies for combating irradiation: a green anti-irradiation approach. Asian Pac J Cancer Prev, 14, 5553-65.
  16. Mahboubi M, Bidgoli FG (2010). Antistaphylococcal activity of Zataria multiflora essential oil and its synergy with vancomycin. Phytomedicine, 17, 548-50.
  17. Maurya DK, Devasagayam TP, Nair CKK (2006). Some novel approaches for radioprotection and the beneficial effect of natural products. Indian J Exp Biol, 44, 93-114.
  18. Park SS, Kim YJ, Ju EJ, et al (2014). Ibulocydine sensitizes human cancers to radiotherapy by induction of mitochondriamediated apoptosis. Radiother Oncol, 112, 295-301.
  19. Ramezani M, Hosseinzadeh H, Samizadeh S (2004). Antinociceptive effects of Zataria multiflora Boiss fractions in mice. J Ethnopharmacol, 91, 167-70.
  20. Saei-Dehkordi SS, Tajik H, Moradi M, et al (2010). Chemical composition of essential oils in Zataria multiflora boiss. from different parts of Iran and their radical scavenging and antimicrobial activity. Food Chem Toxicol, 48, 1562-7.
  21. Sajed H, Sahebkar A, Iranshahi M (2013). Zataria multiflora Boiss. shirazi thyme-an ancient condiment with modern pharmaceutical uses. J Ethnopharmacol, 145, 686-98.
  22. Sebastia N, Almonacid M, Villaescusa JI, et al (2013). Radioprotective activity and cytogenetic effect of resveratrol in human lymphocytes: an in vitro evaluation. Food Cheml Toxicol, 51, 391-5.
  23. Sharififar F, Moshafi M, Mansouri S, et al (2007). In vitro evaluation of antibacterial and antioxidant activities of the essential oil and methanol extract of endemic Zataria multiflora Boiss. Food Control, 18, 800-5.
  24. Shokri H, Asadi F, Bahonar AR, et al (2006). The role of Zataria multiflora essence (Iranian herb) on innate immunity of animal model. Iran J Immunol, 3, 164-8.
  25. Szostak MJ, Kyprianou N (2000). Radiation-induced apoptosis: predictive and therapeutic significance in radiotherapy of prostate cancer (review). Oncol Rep, 7, 699-706.
  26. Vogelstein B, Kinzler KW (2004). Cancer genes and the pathways they control. Nat Med, 10, 789-99.
  27. Wang K, Liu C, Di CJ, et al (2014). Kojic acid protects C57BL/6 mice from gamma-irradiation induced damage. Asian Pac J Cancer Prev, 15, 291-7.
  28. Xu P, Zhang WB, Cai XH, et al (2014). Flavonoids of Rosa roxburghii Tratt act as radioprotectors. Asian Pac J Cancer Prev, 15, 8171-5.
  29. Yao JX, Yao ZF, Li ZF, et al (2014). Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro. Asian Pac J Cancer Prev, 15, 3211-7.
  30. Yao KC, Komata T, Kondo Y, et al (2003). Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of cyclin-dependent kinase inhibitors, and autophagy. J Neurosurg, 98, 378-84.

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