DOI QR코드

DOI QR Code

Induction of Intrinsic and Extrinsic Apoptosis Pathways in the Human Leukemic MOLT-4 Cell Line by Terpinen-4-ol

  • 발행 : 2012.07.31

초록

Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.

키워드

참고문헌

  1. Banjerdpongchai R, Kongtawelert P, Khantamat O, et al (2010). Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells. J Hematol Oncol, 3, 50. https://doi.org/10.1186/1756-8722-3-50
  2. Brunelle JK, Letai A (2009). Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci, 122, 437-41. https://doi.org/10.1242/jcs.031682
  3. Bua-in S, Paisooksantivatana Y (2009). Essential oil and antioxidant activity of aassumunar ginger (zingiberaceae: zingiber montanum (koenig) link ex dietr.) collected from various parts of Thailand. Kasetsart J Natur Sci, 43, 467-75.
  4. Calcabrini A, Stringaro A, Toccacieli L, et al (2004). Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells. J Invest Dermatol, 122, 349-60. https://doi.org/10.1046/j.0022-202X.2004.22236.x
  5. Greay SJ, Ireland DJ, Kissick HT, et al (2010). Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol. Cancer Chemother Pharmacol, 65, 877-88. https://doi.org/10.1007/s00280-009-1093-7
  6. Hart PH, Brand C, Carson CF, et al (2000). Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm Res, 49, 619-26. https://doi.org/10.1007/s000110050639
  7. Jia W, Yu C, Rahmani M, et al (2003). Synergistic antileukemic interactions between 17-AAG and UCN-01 involve interruption of RAF/MEK- and AKT-related pathways. Blood, 102, 1824-32. https://doi.org/10.1182/blood-2002-12-3785
  8. Kang MH, Reynolds CP (2009). Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy. Clin Cancer Res, 15, 1126-32. https://doi.org/10.1158/1078-0432.CCR-08-0144
  9. Lahlou S, Interaminense LF, Leal-Cardoso JH, Duarte GP (2003). Antihypertensive effects of the essential oil of Alpinia zerumbet and its main constituent, terpinen-4-ol, in DOCA-salt hypertensive conscious rats. Fundam Clin Pharmacol, 17, 323-30. https://doi.org/10.1046/j.1472-8206.2003.00150.x
  10. Loughlin R, Gilmore BF, McCarron PA, Tunney MM (2008). Comparison of the cidal activity of tea tree oil and terpinen-4-ol against clinical bacterial skin isolates and human fibroblast cells. Lett Appl Microbiol, 46, 428-33. https://doi.org/10.1111/j.1472-765X.2008.02334.x
  11. Mondello F, De Bernardis F, Girolamo A, Cassone A, Salvatore G (2006). In vivo activity of terpinen-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azole-susceptible and -resistant human pathogenic Candida species. BMC Infect Dis, 6, 158. https://doi.org/10.1186/1471-2334-6-158
  12. Reyes-Zurita FJ, Pachon-Pena G, Lizarraga D, et al (2011). The natural triterpene maslinic acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-dependent mechanism. BMC Cancer, 11, 154. https://doi.org/10.1186/1471-2407-11-154
  13. Schimmer AD, Hedley DW, Penn LZ, Minden MD (2001). Receptor- and mitochondrial-mediated apoptosis in acute leukemia: a translational view. Blood, 98, 3541-53. https://doi.org/10.1182/blood.V98.13.3541
  14. Wu CS, Chen YJ, Chen JJ, et al (2012). Terpinen-4-ol induces apoptosis in human nonsmall cell lung cancer in vitro and in vivo. Evid Based Complement Alternat Med, in press.
  15. Zamzami N, Maisse C, Metivier D, Kroemer G (2007). Measurement of membrane permeability and the permeability transition of mitochondria. Methods Cell Biol, 80, 327-40. https://doi.org/10.1016/S0091-679X(06)80016-6

피인용 문헌

  1. Mono(2-ethylhexyl) phthalate induces apoptosis in p53-silenced L02 cells via activation of both mitochondrial and death receptor pathways vol.30, pp.10, 2015, https://doi.org/10.1002/tox.21990
  2. Apoptosis Induction via ATM Phosphorylation, Cell Cycle Arrest, and ER Stress by Goniothalamin and Chemodrugs Combined Effects on Breast Cancer-Derived MDA-MB-231 Cells vol.2018, pp.2314-6141, 2018, https://doi.org/10.1155/2018/7049053
  3. Alain (Myrtaceae), a species endemic to the Samaná Peninsula, Dominican Republic pp.2163-8152, 2019, https://doi.org/10.1080/10412905.2018.1518275