Synergistic Anti-tumoral Effect of Achillea millefolium Combined with Bleomycin on Prostate Cancer Cells

Background: The aim of this study was to investigate the effec t of methanolic extract of Achillea millefolium L. (MEA) on the antiproliferative activity of bleomycin on human prostate cancer and normal skin cells. Materials and Methods: Human prostate cancer cell (DU-145) and human nonmalignant fibroblast cell (HFFF2) were treated with MEA at various concentrations (20, 100, 500, 1000 and 2000 µg/ml), using bleomycin alone or combined with MEA. Also, the effect of MEA and bleomycin on cell viability was evaluated. Free radical scavenging property was det ermined for this herbal extract. Results: The combination of MEA and bleomycin significantly increased the inhibition of cell growth in cancer cell. The extra ct significantly enhanced cytotoxicity induced by bleomycin showing 60% and 49% survival rate at doses of 1000 and 2000 µg/ml, respectively. In bleomycin-tre ated cells the survival rate reached 85%. MEA did not exhibit any cytotoxicity on HFFF2 cells. Conclusion: This study found that the methanolic extract of Achillea millefolium enhanced the cell toxicity induced by bleomycin in the prostate cancer cell without any significant toxicity on normal cells.

[1]  M. Arababadi,et al.  Effect of aqueous extract of Achillea millefolium on the development of experimental autoimmune encephalomyelitis in C57BL/6 mice , 2014, Indian journal of pharmacology.

[2]  S. E. Rezatofighi,et al.  Evaluating the Efficacy of Achillea millefolium and Thymus vulgaris Extracts Against Newcastle Disease Virus in Ovo , 2014, Jundishapur journal of microbiology.

[3]  E. Düsman,et al.  Antimutagenic Effect of Medicinal Plants Achillea millefolium and Bauhinia forficata In Vivo , 2013, Evidence-based complementary and alternative medicine : eCAM.

[4]  Hosseinimehr Seyed Jalal,et al.  Epicatechin enhances anti-proliferative effect of bleomycin in ovarian cancer cell , 2013 .

[5]  Z. Rabiei,et al.  Antispasmodic effects of yarrow (Achillea millefolium L.) extract in the isolated ileum of rat. , 2013, African journal of traditional, complementary, and alternative medicines : AJTCAM.

[6]  منیره زارعی قادیکلایی,et al.  بررسی ویژگی های فیتوشیمیایی و دارویی گونه بومادران A review on phytochemistry and medicinal properties of the genus Achillea , 2013 .

[7]  Y. Shukla,et al.  Tea polyphenols enhance cisplatin chemosensitivity in cervical cancer cells via induction of apoptosis. , 2013, Life sciences.

[8]  E. Hatzimichael,et al.  Revisiting bleomycin from pathophysiology to safe clinical use. , 2013, Critical reviews in oncology/hematology.

[9]  S. Chou,et al.  Achillea millefolium L. Essential Oil Inhibits LPS-Induced Oxidative Stress and Nitric Oxide Production in RAW 264.7 Macrophages , 2013, International journal of molecular sciences.

[10]  A. Bolzán,et al.  Effect of Thiol Compounds on Bleomycin-Induced DNA and Chromosome Damage in Human Cells , 2013, Archives of environmental & occupational health.

[11]  Q. Shi,et al.  Cytotoxic flavonoids from the flowers of Achillea millefolium , 2013, Chemistry of Natural Compounds.

[12]  Hao Jiang,et al.  Casticin, a flavonoid, potentiates TRAIL-induced apoptosis through modulation of anti-apoptotic proteins and death receptor 5 in colon cancer cells. , 2013, Oncology reports.

[13]  M. Gholivand,et al.  Chemical composition and anxiolytic evaluation of Achillea Wilhelmsii C. Koch essential oil in rat , 2013, Research in pharmaceutical sciences.

[14]  Md. Lutful Amin P-glycoprotein Inhibition for Optimal Drug Delivery , 2013, Drug target insights.

[15]  T. Ozben,et al.  Effects of N-acetyl-L-cysteine on bleomycin induced oxidative stress in malignant testicular germ cell tumors. , 2012, Biochimie.

[16]  T. Ozben,et al.  Effects of curcumin on bleomycin‑induced oxidative stress in malignant testicular germ cell tumors. , 2012, Molecular medicine reports.

[17]  S. Hosseinimehr,et al.  Radioimmunotherapy with ¹³¹I-bevacizumab as a specific molecule for cells with overexpression of the vascular endothelial growth factor. , 2012, Cancer biotherapy & radiopharmaceuticals.

[18]  B. Van Houten,et al.  Mitochondrial DNA-depleted A549 cells are resistant to bleomycin. , 2012, American journal of physiology. Lung cellular and molecular physiology.

[19]  P. Mclaughlin,et al.  Doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy with interferon for advanced stage classic Hodgkin lymphoma: a 10-year follow-up study , 2012, Leukemia & lymphoma.

[20]  Mei Dong,et al.  Achillinin A, a Cytotoxic Guaianolide from the Flower of Yarrow, Achillea millefolium , 2011, Bioscience, biotechnology, and biochemistry.

[21]  S. Hosseinimehr,et al.  The radioprotective effect of Zataria multiflora against genotoxicity induced by γ irradiation in human blood lymphocytes. , 2011, Cancer biotherapy & radiopharmaceuticals.

[22]  P. McKay,et al.  Toxicities associated with bleomycin. , 2010, The journal of the Royal College of Physicians of Edinburgh.

[23]  M. Werner,et al.  Antiulcerogenic activity of hydroalcoholic extract of Achillea millefolium L.: involvement of the antioxidant system. , 2010, Journal of ethnopharmacology.

[24]  Julie Gehl,et al.  Bleomycin treatment of brain tumors: an evaluation. , 2009, Anti-cancer drugs.

[25]  P. Quaglino,et al.  Electrochemotherapy with Intravenous Bleomycin in the Local Treatment of Skin Melanoma Metastases , 2008, Annals of Surgical Oncology.

[26]  Jean Cadet,et al.  Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion , 2007, Proceedings of the National Academy of Sciences.

[27]  T. Yamamoto,et al.  Bleomycin and the skin , 2006, The British journal of dermatology.

[28]  G. Batist,et al.  The flavonoid Casticin has multiple mechanisms of tumor cytotoxicity action. , 2006, Cancer letters.

[29]  A. Gilani,et al.  Studies on hepatoprotective, antispasmodic and calcium antagonist activities of the aqueous‐methanol extract of Achillea millefolium , 2006, Phytotherapy research : PTR.

[30]  D. Kouretas,et al.  Plant phenolics protect from bleomycin-induced oxidative stress and mutagenicity in Salmonella typhimurium TA102. , 2004, Anticancer research.

[31]  M. Farace,et al.  Cellular responses to H(2)O(2) and bleomycin-induced oxidative stress in L6C5 rat myoblasts. , 2003, Free radical biology & medicine.

[32]  L. Chiang,et al.  In vitro anti‐hepatoma activity of fifteen natural medicines from Canada , 2002, Phytotherapy research : PTR.

[33]  T. Kumagai,et al.  Molecular and structural biology of bleomycin and its resistance determinants. , 2002, Journal of bioscience and bioengineering.

[34]  H. Ishii,et al.  Novel antitumor sesquiterpenoids in Achillea millefolium. , 1994, Chemical & pharmaceutical bulletin.

[35]  S. Saeidnia,et al.  A review on phytochemistry and medicinal properties of the genus Achillea , 2011, Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences.

[36]  U. Studer,et al.  Long-term followup results of 1 cycle of adjuvant bleomycin, etoposide and cisplatin chemotherapy for high risk clinical stage I nonseminomatous germ cell tumors of the testis. , 2008, The Journal of urology.

[37]  M. Assadi,et al.  Flora of Iran , 1991 .