Induction of Mitochondrial-Dependent Apoptosis by an Essential Oil from Tanacetum gracile

Abstract

The essential oil of Tanacetum gracile (Accession no. AT-01 termed AT-01 in the manuscript), a cold desert alpine highly aromatic herb, has 40 constituents including lavendulol (21.5 %), lavendulol acetate (1.7 %), α-pinene (11.2 %), 1,8-cineole (15.2 %), cis-β-ocimene (6.9 %), borneol (6.1 %), limonene (5.1 %) and chamazulene (3.7 %). AT-01 was evaluated for its anticancer activity. It inhibited HL-60 cell proliferation with an IC₅₀ of 27 μg/mL. Furthermore, AT-01 induced apoptosis in human leukemia HL-60 cells as measured by several biological end points. AT-01 induced apoptotic body formation, enhanced annexinV-FITC binding of the cells, increased sub-G₀ DNA fraction, loss of mitochondrial membrane potential (Δψ_mt) and release of cytochrome c from mitochondria, activated caspase-9 as well as caspase-3, and increased cleavage of PARP in HL-60 cells. Thus, AT-01 induced apoptosis through the mitochondrial dependant pathway in HL-60 cells.

Tanacetum gracile - Asteraceae - apoptosis - essential oil - cytotoxicity - HL-60

References

• 1 Beauchamp P, Dev V, Kashyap T, Melkani A, Mathela C, Bottini A T. Composition of essential oil of Tanacetum nubigenum Wallich ex DC.  J Essent Oil Res. 2001;  13 319-23
• 2 Nano G M, Bicchi C, Frattini C, Gallino M. Wild Piedmontese plants. II. A rare chemotype of Tanacetum vulgare L., abundant in Piedmont.  Planta Med. 1979;  35 270-4
• 3 Tetenyl P, Kaposi P, Hethelyi E. Variation in essential oils of Tanacetum vulgare.  Photochemistry. 1975;  14 1539-44
• 4 Abad M J, Bermej P, Valverde S, Villar A. Anti inflammatory activity of hydroxyachillin, sesquiterpene lactones from Tanacetum microphyllum.  Planta Med. 1994;  60 228-31
• 5 Souleles C, Stamatakan M. The essential oil from Tanacetum millefolium.  Planta Med. 1991;  57 92
• 6 Gallino M. Essential oil from Tanacetum vulgare growing spontanenously in ”Tierra Fuego” (Argentina).  Planta Med. 1998;  54 182
• 7 Kitchlu S, Bakshi S K, Kaul M K, Bhan M K, Thapa R K, Agarwal S G. A new source of lavandulol from Tanacetum gracile Hook. F & T. Ladakh Himalayas (India).  Flavor Fragr J. 2006;  21 690- 2
• 8 Russin W A, Hoesly J D, Elson C E, Tanner M A, Gould M N. Inhibition of rat mammary carcinogenesis by monoterpenoids.  Carcinogenesis. 1989;  11 2161-4
• 9 Tavera L. Monoterpenes in essential oils. Biosynthesis and properties.  Adv Exp Med Biol. 1999;  464 49-62
• 10 Clerk S S. Perillyl alcohol induces c-Myc-dependent apoptosis in Bcr/Abl-transformed leukemia cells.  Oncology. 2006;  70 8-13
• 11 Ruch R J, Siglar K. Growth inhibition of rat liver epithelial tumor cells by monoterpenes does not involve Ras plasma membrane association.  Carcinogenesis. 1994;  4 787-9
• 12 Heckenkamp J, Leszczynski D, Schiereck J, Kung J, Muraglia G M. Different effects of photodynamic therapy and gamma-irradiation on vascular smooth muscle cells and matrix: implications for inhibiting restenosis.  Arterioscler Thomb Vasc Biol. 1999;  19 2154- 61
• 13 Bhushan S, Singh J, Rao J M, Saxena A K, Qazi G N. A novel lignan composition from Cedrus deodara induces apoptosis and early nitric oxide generation in human leukemia Molt-4 and HL-60 cells.  Nitric Oxide. 2006;  14 72-88
• 14 Krishan A. Rapid flow cytoflourometric analysis of mammalian cell cycle by propidium iodide staining.  J Cell Biol. 1975;  66 188-93
• 15 Crissman H A, Steinkamp J A. Rapid simultaneous measurement of DNA, protein and cell volume in single cells from large mammalian cell populations.  J Cell Biol. 1973;  59 766 -9
• 16 Findley H W, Gu L, Yeager A M, Zhou M. Expression and regulation of Bcl-2, Bcl-xl, and Bax correlate with p53 status and sensitivity to apoptosis in childhood acute lymphoblastic leukemia.  Blood. 1997;  89 2986- 93
• 17 Wang Z, S W ang, Y D ai, S G rant. Bryostatin 1 increases 1-D-arabinofuranosylcytosine-induced cytochome c release and apoptosis in human leukemia cells ectopically expressing Bcl-xL.  JPET. 2002;  301 568-77
• 18 Martins A P, Salgueiro L R, Vila R, Tomi F, Canigueral S, Casanova J. et al . Composition of essential oil of Osicmum canum, O. gratissimum and O. minimum.  Planta Med. 1999;  65 187-9
• 19 Charles D J, Simon J E. A new geraniol chemotype of Osicmum gratissimumL.  J Essent Oil Res. 1992;  4 4231- 4
• 20 Thiantanwat A, Long B J, Bordie A M. Signaling pathways of apoptosis activated by aromatase inhibitiors and antiestrogens.  Cancer Res. 2003;  63 8037-50
• 21 Frankfurt O S, Krishnan A. Apoptosis based drug screening and detection of selective toxicity to cancer cells.  Anticancer Drugs. 2003;  14 555-61
• 22 Yang J, Liu X, Bhalla K, Kim C N, Ibrado A M, Cai J. et al . Prevention of apoptosis by Bcl-2; release of cytochome C from mitochondrial blocked.  Science. 1997;  275 1129-32
• 23 Lazebnik Y A, Kaufmann S H, Desnoyers S, Poirier G G, Earnshaw W C. Cleavage of poly (ADP ribose) polymerase by a proteinase with properties like ICE.  Nature. 1994;  376 346-47
• 24 Tewari M, Quan L T, Rourke K O, Desnoyers S, Zeng Z, Beidler D R. et al . Yama/ CPP32 beta, a mammalian homolog of CED-3, is a Crm A - inhitable proteases that cleaves the death substrate poly (ADP ribose) polymerase.  Cell. 1995;  81 801-9