Abstract
Artemisia lavandulaefolia has been utilized in traditional medicines for the treatment of several diseases. In this study, we attempted to determine whether the essential oil and 1,8-cineole of A. lavandulaefolia induce apoptosis in KB cells. The oil and 1,8-cineole induced the cell death of KB cells as evidenced by the increased cell population in the sub-G1 phase, the appearance of condensed and/or fragmented nuclei, and the generation of a cleaved PARP product. The treatment of the cells with the oil also induced changes in the mitochondrial level of Bcl-2 and Bax, thereby inducing the release of cytochrome c into the cytosol. Furthermore, the oil increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, and p38 MAPK, but 1,8-cineole activated pp38 and pJNK at the same concentrations. These findings show that the mitochondrial and MAPKs pathways might be involved in the oil-induced apoptosis, and may enhance our current understanding of the anticancer functions of the oil to a greater degree than 1,8-cineole.
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References
Cha JD, Jeong MR, Choi HJ, Jeong SI, Moon SE, Yun SI, Kim YH, Kil BS, Song YH. Chemical composition and antimicrobial activity of the essential oil of Artemisia lavandulaefolia. Planta Med. 71: 575–577 (2005)
Kil BS, Lee CH, Kim YS, Yun KY, Yoo HG. Allelopatic effects of A. Lavandulaefolia. Korean J. Ecol. 23: 154–155 (2000)
Robles MAM, West J, Rodriguez E. Recent studies on the zoopharmacognosy, pharmacology, and neurotoxicology of sesquiterpene lactones. Planta Med. 61: 199–203 (1995)
JH P. Korean Folk Medicine. Busan National University Publisher, Busan, Korea. p. 68 1999)
Cha JD, Jeong MR, Kim HY, Lee JC, Lee KY. MAPK activation is necessary to the apoptotic death of KB cells induced by the essential oil isolated from Artemisia iwayomogi. J. Ethnopharmacol. 123: 308–314 (2009)
Ray RS, Ghosh B, Rana A, Chatterjee M. Suppression of cell proliferation, induction of apoptosis, and cell cycle arrest: Chemopreventive activity of vanadium in vivo and in vitro. Int. J. Cancer 120: 13–23 (2007)
Crowell PL. Prevention and therapy of cancer by dietary monoterpenes. J. Nutr. 129: 775S–778S (1999)
Willoughby JA Sr, Sundar SN, Cheung M, Tin AS, Modiano J, Firestone GL. Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclindependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression. J. Biol. Chem. 284: 2203–2213 (2009)
Kim DH, Na HK, Oh TY, Kim WB, Surh YJ. Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces cell cycle arrest in ras-transformed human mammary epithelial cells. Biochem. Pharmacol. 68: 1081–1087 (2004)
Sylvestre M, Pichette A, Longtin A, Nagau F, Legault J. Essential oil analysis and anticancer activity of leaf essential oil of Croton flavens L. from Guadeloupe. J. Ethnopharmacol. 103: 99–102 (2006)
Sylvestre M, Legault J, Dufour D, Pichette A. Chemical composition and anticancer activity of leaf essential oil of Myrica gale L. Phytomedicine 12: 299–304 (2005)
Karioti A, Hadjipavlou-Litina D, Mensah ML, Fleischer TC, Skaltsa H. Composition and antioxidant activity of the essential oils of Xylopia aethiopica (Dun) A. Rich (Annonaceae) leaves, stem bark, root bark, and fresh and dried fruits, growing in Ghana. J. Agr. Food Chem. 52: 8094–8098 (2004)
Wang C, Youle RJ. The role of mitochondria in apoptosis. Annu. Rev. Genet. 43: 95–118 (2009)
Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol. Med. 12: 440–450 (2006)
Gradzka I. Mechanisms and regulation of the programmed cell death. Postepy Biochem. 52: 157–165 (2006)
Norbury CJ, Zhivotovsky B. DNA damage-induced apoptosis. Oncogene 23: 2797–2808 (2004)
White BC, Sullivan JM. Apoptosis. Acad. Emerg. Med. 5: 1019–1029 (1998)
Nalepa G, Zukowska-Szczechowska E. Caspases and apoptosis: Die and let live. Wiad Lek 55: 100–106 (2002)
Koh DW, Dawson TM, Dawson VL. Mediation of cell death by poly (ADP-ribose) polymerase-1. Pharmacol. Res. 52: 5–14 (2005)
Soldani C, Scovassi AI. Poly (ADP-ribose) polymerase-1 cleavage during apoptosis: An update. Apoptosis 7: 321–328 (2002)
Gilmore EC, Nowakowski RS, Caviness VS Jr. Herrup K. Cell birth, cell death, cell diversity, and DNA breaks: How do they all fit together? Trends Neurosci. 23: 100–105 (2000)
Bustamante J, Nutt L, Orrenius S, Gogvadze V. Arsenic stimulates release of cytochrome c from isolated mitochondria via induction of mitochondrial permeability transition. Toxicol. Appl. Pharm. 207: 110–116 (2005)
Andrabi SA, Dawson TM, Dawson VL. Mitochondrial and nuclear cross talk in cell death: Parthanatos. Ann. NY Acad. Sci. 1147: 233–241 (2008)
Czabotar PE, Colman PM, Huang DC. Bax activation by Bim? Cell Death Differ. 16: 1187–1191 (2009)
Er E, Oliver L, Cartron PF, Juin P, Manon S, Vallette FM. Mitochondria as the target of the pro-apoptotic protein Bax. Biochim. Biophys. Acta 1757: 1301–1311 (2006)
Orrenius S. Mitochondrial regulation of apoptotic cell death. Toxicol. Lett. 149: 19–23 (2004)
Kirkin V, Joos S, Zornig M. The role of Bcl-2 family members in tumorigenesis. Biochim. Biophys. Acta 1644: 229–249 (2004)
Stockwin LH, Han B, Yu SX, Hollingshead MG, ElSohly MA, Gul W, Slade D, Galal AM, Newton DL. Artemisinin dimer anticancer activity correlates with heme-catalyzed reactive oxygen species generation and endoplasmic reticulum stress induction. Int. J. Cancer 125: 1266–1275 (2009)
Scorrano L, Korsmeyer SJ. Mechanisms of cytochrome c release by proapoptotic Bcl-2 family members. Biochem. Bioph. Res. Co. 304: 437–444 (2003)
Cho SG, Choi EJ. Apoptotic signaling pathways: Caspases and stress-activated protein kinases. J. Biochem. Mol. Biol. 35: 24–27 (2002)
Cuevas BD, Abell AN, Johnson GL. Role of mitogen-activated protein kinase kinase kinases in signal integration. Oncogene 26: 3159–3171 (2007)
Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23: 2838–2849 (2004)
Edris AE. Anti-cancer properties of Nigella spp. essential oils and their major constituents, thymoquinone, and beta-elemene. Curr. Clin. Pharmacol. 4: 43–46 (2009)
Moteki H, Hibasami H, Yamada Y, Katsuzaki H, Imai K, Komiya T. Specific induction of apoptosis by 1,8-cineole in two human leukemia cell lines, but not a in human stomach cancer cell line. Oncol. Rep. 9: 757–760 (2002)
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Cha, JD., Kim, YH. & Kim, JY. Essential oil and 1,8-cineole from Artemisia lavandulaefolia induces apoptosis in KB cells via mitochondrial stress and caspase activation. Food Sci Biotechnol 19, 185–191 (2010). https://doi.org/10.1007/s10068-010-0025-y
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DOI: https://doi.org/10.1007/s10068-010-0025-y