Mitochondrial and caspase pathways are involved in the induction of apoptosis by nardosinen in MCF-7 breast cancer cell line
Abstract
Natural products isolated from plants provide a valuable source for expansion of new anticancer drugs. Nardosinen (4,9-dihydroxy-nardosin-6-en) is a natural sesquiterpene extracted from Juniperus foetidissima. Recently, we have reported the cytotoxic effects of nardosinen in various cancer cells. The aim of the current study was to investigate the anticancer features of nardosinen as well as its possible molecular mechanisms of the nardosinen cytotoxic effect on breast tumor cells. MTT assay showed that nardosinen notably inhibited cell proliferation in a dose-dependent manner in MCF-7 breast cancer cells. The growth inhibitory effect of nardosinen was associated with the induction of cell apoptosis, activation of caspase-6, increase of reactive oxygen species (ROS), and loss of mitochondrial membrane potentials (ΔΨm). Western blot assay following treatment with nardosinen showed that the expression levels of the Bax were significantly up-regulated and the expression levels of the Bcl-2 were significantly down-regulated. Our results finally exhibited that nardosinen induces apoptosis in breast cancer cells via the mitochondrial and caspase pathways.
Keywords
Full Text:
PDFReferences
Yasemi M, HafeziAhmadi MR, Khajavikhan J, Peyman H, Asadollahi KH, Yasemi MR, Hemati K. An 8 Years Retrospective Study of Breast Cancer Incidence in Ilam Province, Western Iran. J Clin Diagn Res. 2013;7:2923.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7-30.
Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707-16.
Giordano SH, Kuo YF, Freeman JL, Buchholz TA, Hortobagyi GN, Goodwin JS. Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst. 2005;97(6):419-24.
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687-717.
Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003;362:419-27.
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371-88.
Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359:2131-9.
Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol. 2005;100(1-2): 72-79.
Marcysiak K, Mazur M, Romo A, Montserrat JM, Didukh Y, Boratynska K, et al. Numerical taxonomy of Juniperus thurifera, J. excelsa and J. foetidissima (Cupressaceae) based on morphological characters. Bot J Linn Soc. 2007;155:483-495.
Sadeghi-aliabadi H, Emami A, Saidi M, Sadeghi B, Jafarian A. Evaluation of in vitro cytotoxic effects of Juniperus foetidissima and Juniperus sabina extracts against a panel of cancer cells. Iran J Pharm Res. 2010;20:281-286.
Lesjak MM, Beara IN, Orčić DZ, Ristić JD, Anačkov GT, Božin BN, Mimica-Dukić NM. Chemical characterisation and biological effects of Juniperus foetidissima Willd. 1806. LWT-Food SCI Technol. 2013;53:530-539.
Murakami A, Takahashi D, Kinoshita T, Koshimizu K, Kim HW, Yoshihiro A, et al. Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite. Carcinogenesis. 2002;23:795-802.
Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT. The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells. Blood. 2005;105:4163-4169.
Murakami A, Tanaka T, Lee JY, Surh YJ, Kim HW, Kawabata K, et al. Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice. Int J Cancer. 2004;110:481-490.
Zhang S, Won YK, Ong CN, Shen HM. Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms. Curr Med Chem Anticancer Agents. 2005;5:239-249.
Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495-516.
Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998;281:1312-1316.
Fingrut O, Flescher E. Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells. Leukemia. 2002;16(4):608-616.
Hamzeloo-Moghadam M, Aghaei M, Fallahian F, Jafari SM, Dolati M, Abdolmohammadi MH, et al. Britannin, a sesquiterpene lactone, inhibits proliferation and induces apoptosis through the mitochondrial signaling pathway in human breast cancer cells. Tumor Biol. 2015;36:1191-1198.
Rafieian-kopaei M, Suleimanidehkordi I, Ghanadian M, Shokrollahi A, Aghaei M, Syed Majid A, et al.. Bioactivity-guided isolation of new antiproliferative compounds from Juniperus foetidissima Willd. Natural Product Research. 2016;30:1927-1933.
Joshaghani HR, Jafari SM, Aghaei M, Panjehpour M, Abedi H. A3 adenosine receptor agonist induce G1 cell cycle arrest via Cyclin D and cyclin-dependent kinase 4 pathways in OVCAR-3 and Caov-4 cell lines. J Cancer Res Ther. 2017;13:107-112
Jafari SM, Panjehpour M, Aghaei M, Joshaghani HR, Enderami SE. A3 adenosine receptor agonist inhibited survival of breast cancer stem cells via GLI-1 and ERK1/2 pathway. J Cell Biochem. 2017. doi: 10.1002/jcb.25945. [Epub ahead of print]
Hajiahmadi S, Panjehpour M, Aghaei M, Mousavi S. Molecular expression of adenosine receptors in OVCAR-3, Caov-4 and SKOV-3 human ovarian cancer cell lines. Res Pharm Sci. 2015;10(1):43-51.
Azemikhah M, Ashtiani HA, Aghaei M, Rastegar H. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues. Res Pharm Sci. 2015;10:356-363.
Jafari SM, Panjehpour M, Aghaei M, Joshaghani HR, Zargar BalajamN. Apoptosis and cell cycle regulatory effects of adenosine by modulation of GLI-1 and ERK1/2 pathways in CD44+ and CD24− breast cancer stem cells. . Cell Prolif. 2017. doi: 10.1111/cpr.12345. [Epub ahead of print]
Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1-22.
Greenwell M, Rahman PK. Medicinal plants: their use in anticancer treatment. Int J Pharm Sci Res. 2015;6:4103–4112.
Safarzadeh E, Sandoghchian Shotorbani S, & Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 2014;4(Suppl 1):421–427.
Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and molecular targeting therapy in cancer. Biomed Res Int. 2014;2014:150845.
Riedl S, Rinner B, Asslaber M, Schaider H, Walzer S, Novak A, et al. In search of a novel target - phosphatidylserine exposed by non-apoptotic tumor cells and metastases of malignancies with poor treatment efficacy. Biochim Biophys Acta. 2011;1808(11):2638-2645.
Steele AJ, Jones DT, Ganeshaguru K, Duke VM, Yogashangary BC, North JM, et al. The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro. Leukemia. 2006;20(6):1073-1079.
Lincz LF. Deciphering the apoptotic pathway: all roads lead to death. Immunol Cell Biol. 1998;76(1):1-9.
Aghaei M, Panjehpour M, Karami-Tehrani F, Salami S. Molecular mechanisms of A3 adenosine receptor-induced G1 cell cycle arrest and apoptosis in androgen-dependent and independent prostate cancer cell lines: involvement of intrinsic pathway. J Cancer Res Clin Oncol. 2011;137:1511-1523.
McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5: a008656.
Aghaei M, Karami‐Tehrani F, Panjehpour M, Salami S, Fallahian F. Adenosine induces cell‐cycle arrest and apoptosis in androgen‐dependent and‐independent prostate cancer cell lines, LNcap‐FGC‐10, DU‐145, and PC3. Prostate. 2012;72:361-75.
Oropesa-Avila M, Andrade-Talavera Y, Garrido-Maraver J, Cordero MD, de la Mata M, Cotan D, et al. Stabilization of apoptotic cells: generation of zombie cells. Cell Death Dis. 2014;5:e1369.
Khan M, Ding C, Rasul A, Yi F, Li T, Gao H, et al. Isoalantolactone induces reactive oxygen species mediated apoptosis in pancreatic carcinoma PANC-1 cells. Int J Biol Sci. 2012;8:533–547.
Yang F, Chen WD, Deng R, Zhang H, Tang J, Wu KW, et al. Hirsutanol A, a novel sesquiterpene compound from fungus Chondrostereum sp., induces apoptosis and inhibits tumor growth through mitochondrial-independent ROS production: Hirsutanol A inhibits tumor growth through ROS production. J Transl Med. 2013;11; 32.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.