Issue
Ferula gummosa gum induces apoptosis via ROS mechanism in human leukemic cells
Corresponding Author(s) : Azar Hosseini
Cellular and Molecular Biology,
Vol. 63 No. 11: Issue 11
Abstract
Ferula species known for its oleo-resins that are recognized valuable industrial crops and food products. In this study, we examined the level of cellular oxidants, cytotoxicity, apoptosis and differentiation induced by oleo resin gum from Ferula gummosa (30-250 µg/mL), as well as Arsenic trioxide (50 µM, as positive control), in leukemic (NB4 and HL-60 cells) and normal polymorph nuclear cells during 72 h. Resazurin assay was used to determine cell viability following treatment with F. gummosa (30-250 µg/mL). Intracellular reactive oxygen species was measured by fluorimetry using carboxy 2"², 7"²-dichlorofluorescein diacetate. Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). Differentiation of cells evaluated by Giemsa staining and Nitro Blue Tetrazolium reduction. F. gummosa showed a concentration-dependent suppression in cell survival with IC50 values of 41.8 µg/mL for HL60 and 59.2 µg/mL for NB4 cells after 72 h treatment. ROS formation and apoptotic cells were concentration-dependently increased following treatment with F. gummosa, similar to As2O3. F. gummosa did not induce differentiation of leukemic cells towards granulocytic pattern. The resin did not have toxic effect on PMN cells (<800 µg/mL). In conclusion, the present study demonstrated that F. gummosa induced apoptosis through ROS mechanism on leukemic cells as a concentration and time dependent manner. The precise signaling pathway by which F. gummosa induce apoptosis needs further research.
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- Kolahdoozan S, Sadjadi A, Radmard AR, Khademi H. Five common cancers in Iran. Arch Iran Med. 2010; 13: 143.
- Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Annals of Oncology. 2009; 20: 556-63.
- Goss PE, Strasser-Weippl K, Lee-Bychkovsky BL, Fan L, Li J, Chavarri-Guerra Y, et al. Challenges to effective cancer control in China, India, and Russia. The Lancet Oncology. 2014; 15: 489-538.
- Zhang TD, Chen GQ, Wang ZG, Wang ZY, Chen SJ, Chen Z. Arsenic trioxide, a therapeutic agent for APL. Oncogene. 2001 Oct 29; 20: 7146-53.
- Liu J-J, Hu T, Wu X-Y, Wang C-Z, Xu Y, Zhang Y, et al. Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone–Induced Apoptosis in Leukemia K562 Cells and Its Mechanisms of Action. Int J Toxicol. 2009; 28: 123-31.
- Warner NL, Moore MA, Metcalf D. A transplantable myelomonocytic leukemia in BALB/c mice: cytology, karyotype, and muramidase content. J Natl Cancer Inst. 1969; 43: 963-82.
- Choi E-S, Cho S-D, Jeon J-G, Cho N-P. The apoptotic effect of the hexane extract of Rheum undulatum L. in oral cancer cells through the down-regulation of specificity protein 1 and survivin. Laboratory animal research. 2011; 27: 19-24.
- Hsieh Y-J, Chang C-J, Wan C-F, Chen C-P, Chiu Y-H, Leu Y-L, et al. Euphorbia formosana root extract induces apoptosis by caspase-dependent cell death via fas and mitochondrial pathway in THP-1 human leukemic cells. Molecules. 2013; 18: 1949-62.
- Abdullah TH, Kandil O, Elkadi A, Carter J. Garlic revisited: therapeutic for the major diseases of our times? J Natl Med Assoc. 1988; 80: 439.
- Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Sukari MA, Abdullah R, et al. Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo. Leuk Res. 2010; 34: 1483-92.
- Ghasemi Y, Faridi P, Mehregan I, Mohagheghzadeh A. Ferula gummosa fruits: an aromatic antimicrobial agent. Chemistry of natural compounds. 2005; 41: 311-4.
- Mantell C. The natural hard resins”their botany, sources and utilization. Econ Bot. 1950; 4: 203-42.
- Panda H. Herbal Soaps & Detergents Hand Book: NATIONAL INSTITUTE OF INDUSTRIAL RE; 2003.
- Mortazaienezhad F, Sadeghian M. Investigation of compounds from galbanum (Ferula gummosa) boiss. Asian Journal of Plant Sciences. 2006.
- Howlett M. Clouding agents for use in beverages. 1980.
- Javidnia K, Miri R, Kamalinejad M, Edraki N. Chemical composition of Ferula persica Wild. essential oil from Iran. Flavour Fragrance J. 2005; 20: 605-6.
- Mohammadzadeh Milani J, Emam-Djomeh Z, Safari M, Mousavi M, Ghanbarzadeh B, Philips GO. Physicochemical and emulsifying properties of Barijeh (Ferula gumosa) gum. Iranian Journal of Chemistry and Chemical Engineering (IJCCE). 2007; 26: 81-8.
- Asili J, Sahebkar A, Bazzaz BSF, Sharifi S, Iranshahi M. Identification of essential oil components of Ferula badrakema fruits by GC-MS and 13C-NMR methods and evaluation of its antimicrobial activity. Journal of Essential Oil Bearing Plants. 2009; 12: 7-15.
- Habibi Z, Salehi P, Yousefi M, Hejazi Y, Laleh A, Mozaffarian V, et al. Chemical composition and antimicrobial activity of the essential oils of Ferula latisecta and Mozaffariania insignis from Iran. Chemistry of natural compounds. 2006; 42: 689-92.
- Cassatella M, Cappelli R, Della Bianca V, Grzeskowiak M, Dusi S, Berton G. Interferon-gamma activates human neutrophil oxygen metabolism and exocytosis. Immunology. 1988; 63: 499.
- Mashkani B, Tanipour MH, Saadatmandzadeh M, Ashman LK, Griffith R. FMS-like tyrosine kinase 3 (FLT3) inhibitors: Molecular docking and experimental studies. Eur J Pharmacol. 2016; 776: 156-66.
- Hosseini A, Rajabian A. Protective effect of Rheum turkestanikum root against doxorubicin-induced toxicity in H9c2 cells. Revista Brasileira de Farmacognosia. 2016; 26: 347-51.
- Bakhtiari E, Hosseini A, Boroushaki MT, Mousavi SH. Synergistic, cytotoxic and apoptotic activities of olmesartan with NF-κB inhibitor against HeLa human cell line. Toxicol Mech Methods. 2015; 25: 614-21.
- Yan H, Peng Z-G, Wu Y-L, Jiang Y, Yu Y, Huang Y, et al. Hypoxia-simulating agents and selective stimulation of arsenic trioxide-induced growth arrest and cell differentiation in acute promyelocytic leukemic cells. Haematologica. 2005; 90: 1607-16.
- Gupta K, Stefan T, Ignatz-Hoover J, Moreton S, Parizher G, Saunthararajah Y, et al. GSK-3 inhibition sensitizes acute myeloid leukemia cells to 1, 25D-mediated differentiation. Cancer Res. 2016; 76: 2743-53.
- Ghorbani A, Rajaei Z, Zendehbad SB. Effects of fenugreek seeds on adipogenesis and lipolysis in normal and diabetic rats. Pak J Biol Sci. 2014; 17: 523.
- Wollgast J, Anklam E. Review on polyphenols in Theobroma cacao: changes in composition during the manufacture of chocolate and methodology for identification and quantification. Food Res Int. 2000; 33: 423-47.
- Madhavi D, Deshpande S, Salunkhe DK. Food antioxidants: Technological: Toxicological and health perspectives: CRC Press; 1995.
- Sadeghnia HR, Ghorbani Hesari T, Mortazavian SM, Mousavi SH, Tayarani-Najaran Z, Ghorbani A. Viola tricolor induces apoptosis in cancer cells and exhibits antiangiogenic activity on chicken chorioallantoic membrane. BioMed Research International. 2014; 2014.
- Upur H, Yusup A, Baudrimont I, Umar A, Berke B, Yimit D, et al. Inhibition of cell growth and cellular protein, DNA and RNA synthesis in human hepatoma (HepG2) cells by ethanol extract of abnormal Savda Munziq of traditional Uighur medicine. Evid Based Complement Alternat Med. 2011; 2011.
- Estañ MC, Calviño E, Calvo S, Guillén-Guío B, del Carmen Boyano-Adanez M, de Blas E, et al. Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities. PLoS One. 2014; 9: e115250.
- Suganuma K, Miwa H, Imai N, Shikami M, Gotou M, Goto M, et al. Energy metabolism of leukemia cells: glycolysis versus oxidative phosphorylation. Leuk Lymphoma. 2010; 51: 2112-9.
- Gudarzi H, Salimi M, Irian S, Amanzadeh A, Mostafapour Kandelous H, Azadmanesh K, et al. Ethanolic extract of Ferula gummosa is cytotoxic against cancer cells by inducing apoptosis and cell cycle arrest. Nat Prod Res. 2015; 29: 546-50.
- Askari M, Sahebkar A, Iranshahi M. Synthesis and purification of 7-prenyloxycoumarins and herniarin as bioactive natural coumarins. Iranian Journal of Basic Medical Sciences. 2009; 12: 63-9.
- Shahverdi A, Saadat F, Khorramizadeh M, Iranshahi M, Khoshayand M. Two matrix metalloproteinases inhibitors from Ferula persica var. persica. Phytomedicine. 2006; 13: 712-7.
- Iranshahi M, Sahebkar A, Takasaki M, Konoshima T, Tokuda H. Cancer chemopreventive activity of the prenylated coumarin, umbelliprenin, in vivo. Eur J Cancer Prev. 2009; 18: 412-5.
- Iranshahi M, Askari M, Sahebkar A, Adjipavlou-Litina D. Evaluation of antioxidant, anti-inflammatory and lipoxygenase inhibitory activities of the prenylated coumarin umbelliprenin. DARU Journal of Pharmaceutical Sciences. 2015; 17: 99-103.
- Barthomeuf C, Lim S, Iranshahi M, Chollet P. Umbelliprenin from Ferula szowitsiana inhibits the growth of human M4Beu metastatic pigmented malignant melanoma cells through cell-cycle arrest in G1 and induction of caspase-dependent apoptosis. Phytomedicine. 2008; 15: 103-11.
- Merfort I. Perspectives on sesquiterpene lactones in inflammation and cancer. Curr Drug Targets. 2011; 12: 1560-73.
References
Kolahdoozan S, Sadjadi A, Radmard AR, Khademi H. Five common cancers in Iran. Arch Iran Med. 2010; 13: 143.
Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Annals of Oncology. 2009; 20: 556-63.
Goss PE, Strasser-Weippl K, Lee-Bychkovsky BL, Fan L, Li J, Chavarri-Guerra Y, et al. Challenges to effective cancer control in China, India, and Russia. The Lancet Oncology. 2014; 15: 489-538.
Zhang TD, Chen GQ, Wang ZG, Wang ZY, Chen SJ, Chen Z. Arsenic trioxide, a therapeutic agent for APL. Oncogene. 2001 Oct 29; 20: 7146-53.
Liu J-J, Hu T, Wu X-Y, Wang C-Z, Xu Y, Zhang Y, et al. Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone–Induced Apoptosis in Leukemia K562 Cells and Its Mechanisms of Action. Int J Toxicol. 2009; 28: 123-31.
Warner NL, Moore MA, Metcalf D. A transplantable myelomonocytic leukemia in BALB/c mice: cytology, karyotype, and muramidase content. J Natl Cancer Inst. 1969; 43: 963-82.
Choi E-S, Cho S-D, Jeon J-G, Cho N-P. The apoptotic effect of the hexane extract of Rheum undulatum L. in oral cancer cells through the down-regulation of specificity protein 1 and survivin. Laboratory animal research. 2011; 27: 19-24.
Hsieh Y-J, Chang C-J, Wan C-F, Chen C-P, Chiu Y-H, Leu Y-L, et al. Euphorbia formosana root extract induces apoptosis by caspase-dependent cell death via fas and mitochondrial pathway in THP-1 human leukemic cells. Molecules. 2013; 18: 1949-62.
Abdullah TH, Kandil O, Elkadi A, Carter J. Garlic revisited: therapeutic for the major diseases of our times? J Natl Med Assoc. 1988; 80: 439.
Mohan S, Abdul AB, Abdelwahab SI, Al-Zubairi AS, Sukari MA, Abdullah R, et al. Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo. Leuk Res. 2010; 34: 1483-92.
Ghasemi Y, Faridi P, Mehregan I, Mohagheghzadeh A. Ferula gummosa fruits: an aromatic antimicrobial agent. Chemistry of natural compounds. 2005; 41: 311-4.
Mantell C. The natural hard resins”their botany, sources and utilization. Econ Bot. 1950; 4: 203-42.
Panda H. Herbal Soaps & Detergents Hand Book: NATIONAL INSTITUTE OF INDUSTRIAL RE; 2003.
Mortazaienezhad F, Sadeghian M. Investigation of compounds from galbanum (Ferula gummosa) boiss. Asian Journal of Plant Sciences. 2006.
Howlett M. Clouding agents for use in beverages. 1980.
Javidnia K, Miri R, Kamalinejad M, Edraki N. Chemical composition of Ferula persica Wild. essential oil from Iran. Flavour Fragrance J. 2005; 20: 605-6.
Mohammadzadeh Milani J, Emam-Djomeh Z, Safari M, Mousavi M, Ghanbarzadeh B, Philips GO. Physicochemical and emulsifying properties of Barijeh (Ferula gumosa) gum. Iranian Journal of Chemistry and Chemical Engineering (IJCCE). 2007; 26: 81-8.
Asili J, Sahebkar A, Bazzaz BSF, Sharifi S, Iranshahi M. Identification of essential oil components of Ferula badrakema fruits by GC-MS and 13C-NMR methods and evaluation of its antimicrobial activity. Journal of Essential Oil Bearing Plants. 2009; 12: 7-15.
Habibi Z, Salehi P, Yousefi M, Hejazi Y, Laleh A, Mozaffarian V, et al. Chemical composition and antimicrobial activity of the essential oils of Ferula latisecta and Mozaffariania insignis from Iran. Chemistry of natural compounds. 2006; 42: 689-92.
Cassatella M, Cappelli R, Della Bianca V, Grzeskowiak M, Dusi S, Berton G. Interferon-gamma activates human neutrophil oxygen metabolism and exocytosis. Immunology. 1988; 63: 499.
Mashkani B, Tanipour MH, Saadatmandzadeh M, Ashman LK, Griffith R. FMS-like tyrosine kinase 3 (FLT3) inhibitors: Molecular docking and experimental studies. Eur J Pharmacol. 2016; 776: 156-66.
Hosseini A, Rajabian A. Protective effect of Rheum turkestanikum root against doxorubicin-induced toxicity in H9c2 cells. Revista Brasileira de Farmacognosia. 2016; 26: 347-51.
Bakhtiari E, Hosseini A, Boroushaki MT, Mousavi SH. Synergistic, cytotoxic and apoptotic activities of olmesartan with NF-κB inhibitor against HeLa human cell line. Toxicol Mech Methods. 2015; 25: 614-21.
Yan H, Peng Z-G, Wu Y-L, Jiang Y, Yu Y, Huang Y, et al. Hypoxia-simulating agents and selective stimulation of arsenic trioxide-induced growth arrest and cell differentiation in acute promyelocytic leukemic cells. Haematologica. 2005; 90: 1607-16.
Gupta K, Stefan T, Ignatz-Hoover J, Moreton S, Parizher G, Saunthararajah Y, et al. GSK-3 inhibition sensitizes acute myeloid leukemia cells to 1, 25D-mediated differentiation. Cancer Res. 2016; 76: 2743-53.
Ghorbani A, Rajaei Z, Zendehbad SB. Effects of fenugreek seeds on adipogenesis and lipolysis in normal and diabetic rats. Pak J Biol Sci. 2014; 17: 523.
Wollgast J, Anklam E. Review on polyphenols in Theobroma cacao: changes in composition during the manufacture of chocolate and methodology for identification and quantification. Food Res Int. 2000; 33: 423-47.
Madhavi D, Deshpande S, Salunkhe DK. Food antioxidants: Technological: Toxicological and health perspectives: CRC Press; 1995.
Sadeghnia HR, Ghorbani Hesari T, Mortazavian SM, Mousavi SH, Tayarani-Najaran Z, Ghorbani A. Viola tricolor induces apoptosis in cancer cells and exhibits antiangiogenic activity on chicken chorioallantoic membrane. BioMed Research International. 2014; 2014.
Upur H, Yusup A, Baudrimont I, Umar A, Berke B, Yimit D, et al. Inhibition of cell growth and cellular protein, DNA and RNA synthesis in human hepatoma (HepG2) cells by ethanol extract of abnormal Savda Munziq of traditional Uighur medicine. Evid Based Complement Alternat Med. 2011; 2011.
Estañ MC, Calviño E, Calvo S, Guillén-Guío B, del Carmen Boyano-Adanez M, de Blas E, et al. Apoptotic efficacy of etomoxir in human acute myeloid leukemia cells. Cooperation with arsenic trioxide and glycolytic inhibitors, and regulation by oxidative stress and protein kinase activities. PLoS One. 2014; 9: e115250.
Suganuma K, Miwa H, Imai N, Shikami M, Gotou M, Goto M, et al. Energy metabolism of leukemia cells: glycolysis versus oxidative phosphorylation. Leuk Lymphoma. 2010; 51: 2112-9.
Gudarzi H, Salimi M, Irian S, Amanzadeh A, Mostafapour Kandelous H, Azadmanesh K, et al. Ethanolic extract of Ferula gummosa is cytotoxic against cancer cells by inducing apoptosis and cell cycle arrest. Nat Prod Res. 2015; 29: 546-50.
Askari M, Sahebkar A, Iranshahi M. Synthesis and purification of 7-prenyloxycoumarins and herniarin as bioactive natural coumarins. Iranian Journal of Basic Medical Sciences. 2009; 12: 63-9.
Shahverdi A, Saadat F, Khorramizadeh M, Iranshahi M, Khoshayand M. Two matrix metalloproteinases inhibitors from Ferula persica var. persica. Phytomedicine. 2006; 13: 712-7.
Iranshahi M, Sahebkar A, Takasaki M, Konoshima T, Tokuda H. Cancer chemopreventive activity of the prenylated coumarin, umbelliprenin, in vivo. Eur J Cancer Prev. 2009; 18: 412-5.
Iranshahi M, Askari M, Sahebkar A, Adjipavlou-Litina D. Evaluation of antioxidant, anti-inflammatory and lipoxygenase inhibitory activities of the prenylated coumarin umbelliprenin. DARU Journal of Pharmaceutical Sciences. 2015; 17: 99-103.
Barthomeuf C, Lim S, Iranshahi M, Chollet P. Umbelliprenin from Ferula szowitsiana inhibits the growth of human M4Beu metastatic pigmented malignant melanoma cells through cell-cycle arrest in G1 and induction of caspase-dependent apoptosis. Phytomedicine. 2008; 15: 103-11.
Merfort I. Perspectives on sesquiterpene lactones in inflammation and cancer. Curr Drug Targets. 2011; 12: 1560-73.