Pinus densiflora leaf essential oil induces apoptosis via ROS generation and activation of caspases in YD-8 human oral cancer cells

Jo,Jeong-Rang; Park,Ju  Sung; Park,Yu-Kyοung; Chae,Young  Zoo; Lee,Gyu-Hee; Park,Gy-Young; Jang,Byeong-Churl

doi:10.3892/ijo.2011.1263

Pinus densiflora leaf essential oil induces apoptosis via ROS generation and activation of caspases in YD-8 human oral cancer cells

Authors:
- Jeong-Rang Jo
- Ju Sung Park
- Yu-Kyοung Park
- Young Zoo Chae
- Gyu-Hee Lee
- Gy-Young Park
- Byeong-Churl Jang
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Affiliations: Department of Medical Genetic Engineering, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea , Department of Medical Genetic Engineering, Keimyung University School of Medicine, 2800 Shindang-dong, Dalseo-gu, Daegu 704-701, Republic of Korea
Published online on: November 11, 2011 https://doi.org/10.3892/ijo.2011.1263
Pages: 1238-1245

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Abstract

The leaf of Pinus (P.) densiflora, a pine tree widely distributed in Asian countries, has been used as a traditional medicine. In the present study, we investigated the anticancer activity of essential oil, extracted by steam distillation, from the leaf of P. densiflora in YD-8 human oral squamous cell carcinoma (OSCC) cells. Treatment of YD-8 cells with P. densiflora leaf essential oil (PLEO) at 60 µg/ml for 8 h strongly inhibited proliferation and survival and induced apoptosis. Notably, treatment with PLEO led to generation of ROS, activation of caspase-9, PARP cleavage, down-regulation of Bcl-2, and phosphorylation of ERK-1/2 and JNK-1/2 in YD-8 cells. Treatment with PLEO, however, did not affect the expression of Bax, XIAP and GRP78. Importantly, pharmacological inhibition studies demonstrated that treatment with vitamin E (an anti-oxidant) or z-VAD-fmk (a pan-caspase inhibitor), but not with PD98059 (an ERK-1/2 inhibitor) or SP600125 (a JNK-1/2 inhibitor), strongly suppressed PLEO-induced apoptosis in YD-8 cells and reduction of their survival. Vitamin E treatment further blocked activation of caspase-9 and Bcl-2 down-regulation induced by PLEO. Thus, these results demonstrate firstly that PLEO has anti-proliferative, anti-survival and pro-apoptotic effects on YD-8 cells and the effects are largely due to the ROS-dependent activation of caspases.

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1	Zain RB: Cultural and dietary risk factors of oral cancer and precancer - a brief overview. Oral Oncol. 37:205–210. 2001. View Article : Google Scholar : PubMed/NCBI
2	Claus F, Duthoy W, Boterberg T, et al: Intensity modulated radiation therapy for oropharyngeal and oral cavity tumors: clinical use and experience. Oral Oncol. 38:597–604. 2002. View Article : Google Scholar : PubMed/NCBI
3	Nakazawa M, Ohnishi T, Ohmae M, et al: Phase II study of a novel oral formation of 5-fluorouracil in combination with low-dose cisplatin as preoperative chemotherapy of oral squamous cell carcinoma. Int J Clin Pharmacol Res. 25:115–122. 2005.PubMed/NCBI
4	Wyllie AH, Kerr JF and Currie AR: Cell death: the significance of apoptosis. Int Rev Cytol. 68:251–306. 1980. View Article : Google Scholar
5	Cohen GM: Caspases: the executioners of apoptosis. Biochem J. 326:1–16. 1997.
6	Adams JM and Cory S: The Bcl-2 protein family: arbiters of cell survival. Science. 281:1322–1326. 1998. View Article : Google Scholar : PubMed/NCBI
7	Deveraux QL and Reed JC: IAP family proteins - suppressors of apoptosis. Genes Dev. 13:239–252. 1999. View Article : Google Scholar : PubMed/NCBI
8	Van Themsche C, Chaudhry P, Leblanc V, et al: XIAP gene expression and function is regulated autocrine and paracrine TGF-beta signaling. Mol Cancer. 9:2162010.PubMed/NCBI
9	Fleury C, Mignotte B and Vayssiere JL: Mitochondrial reactive oxygen species in cell death signaling. Biochimie. 84:131–141. 2002. View Article : Google Scholar : PubMed/NCBI
10	Simon HU, Haj-Yehia A and Levi-Schaffer F: Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 5:415–418. 2000. View Article : Google Scholar : PubMed/NCBI
11	Groenendyk J and Michalak M: Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol. 52:381–395. 2005.PubMed/NCBI
12	Huang X, Zhang Z, Jia L, et al: Endoplasmic reticulum stress contributes to vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells. Cancer Lett. 296:123–131. 2010. View Article : Google Scholar : PubMed/NCBI
13	Feuerstein GZ and Young PR: Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways. Cardiovasc Res. 45:560–569. 2000. View Article : Google Scholar : PubMed/NCBI
14	Lucas M and Sánchez-Margalet V: Protein kinase C involvement in apoptosis. Gen Pharmacol. 26:881–887. 1995. View Article : Google Scholar
15	Bakkali F, Averbeck S, Averbeck D, et al: Biological effects of essential oils - a review. Food Chem Toxicol. 46:446–475. 2008. View Article : Google Scholar : PubMed/NCBI
16	Hajhashemi V, Ghannadi A and Sharif B: Anti-inflammatory and analgesic properties of the leaf extracts and essential oil of Lavandula angustifolia Mill. J Ethnopharmacol. 89:67–71. 2003. View Article : Google Scholar : PubMed/NCBI
17	Perry NS, Bollen C, Perry EK, et al: Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav. 75:651–659. 2003. View Article : Google Scholar : PubMed/NCBI
18	Silva J, Abebe W, Sousa SM, et al: Analgesic and anti-inflammatory effects of essential oils of Eucalyptus. J Ethnopharmacol. 89:277–283. 2003. View Article : Google Scholar : PubMed/NCBI
19	Sylvestre M, Legault J, Dufour D, et al: Chemical composition and anticancer activity of leaf essential oil of Myrica gale L. Phytomedicine. 12:299–304. 2005. View Article : Google Scholar : PubMed/NCBI
20	Manosroi J, Dhumtanom P and Manosroi A: Anti-proliferative activity of essential oil extracted from thai medicinal plants on KB and P388 cell lines. Cancer Lett. 235:114–120. 2006. View Article : Google Scholar : PubMed/NCBI
21	Wei FX, Li MY, Song YH, et al: Apoptosis and activity changes of telomerase induced by essential oil from pine needles in HepG2 cell line. Zhong Yao Cai. 31:1197–1200. 2008.PubMed/NCBI
22	Kim KY and Chung HJ: Flavor compounds of pine sprout tea and pine needle tea. J Agric Food Chem. 48:1269–1272. 2000. View Article : Google Scholar : PubMed/NCBI
23	Allen RT, Hunter WJ III and Agrawal DK: Morphological and biochemical characterization and analysis of apoptosis. J Pharmacol Toxicol Methods. 37:215–228. 1997. View Article : Google Scholar : PubMed/NCBI
24	Paik SY, Koh KH, Beak SM, et al: The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of HepG2 human hepatoma cells through increased production of reactive oxygen species. Biol Pharm Bull. 28:802–807. 2005.PubMed/NCBI
25	Xiao Y, Yang FQ, Li SP, et al: Essential oil of Curcuma wenyujin induces apoptosis in human hepatoma cells. World J Gastroenterol. 14:4309–4318. 2008.
26	Cha JD, Jeong MR, Kim HY, et al: 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. View Article : Google Scholar : PubMed/NCBI
27	Emoto Y, Manome Y, Meinhardt G, et al: Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells. EMBO J. 14:6148–6156. 1995.PubMed/NCBI
28	Lazebnik YA, Kaufmann SH, Desnoyers S, et al: Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 371:346–347. 1994. View Article : Google Scholar : PubMed/NCBI
29	Festjens N, Mvan Gurp M, van Loo G, et al: Bcl-2 family members as sentinels of cellular integrity and role of mitochondrial intermembrane space proteins in apoptotic cell death. Acta Haematol. 111:7–27. 2004. View Article : Google Scholar : PubMed/NCBI
30	Borner C: The Bcl-2 protein family: sensor and checkpoints for life-or-death decisions. Mol Immunol. 39:615–647. 2003. View Article : Google Scholar : PubMed/NCBI
31	De Vincente JC, Olay S, Lequerica-Fernandez P, et al: Expression of Bcl-2 but not Bax has a prognostic significance in tongue carcinoma. J Oral Pathol Med. 35:140–145. 2006.
32	Kato K, Kawashiri S, Yoshizawa K, et al: Apoptosis-associated markers and clinical outcome in human oral squamous cell carcinomas. J Oral Pathol Med. 37:364–371. 2008. View Article : Google Scholar : PubMed/NCBI
33	Zhang B, Gojo I and Fenton RG: Myeloid cell factor-1 is a critical survival factor for multiple myeloma. Blood. 99:1885–1893. 2002. View Article : Google Scholar : PubMed/NCBI
34	Deveraux QL, Takahashi R, Salvesen GS, et al: X-linked IAP is a direct inhibitor of cell-death proteases. Nature. 388:300–304. 1997. View Article : Google Scholar : PubMed/NCBI
35	Shiozaki EN, Chai J, Rigotti DJ, et al: Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell. 11:519–527. 2003. View Article : Google Scholar : PubMed/NCBI
36	Troppmair J, Bruder JT, Munoz H, et al: Mitogen-activated protein kinase/extracellular signal-regulated protein kinase activation by oncogenes, serum, and 12-O tetradecanoylphorbol-13-acetate requires Raf and is necessary for transformation. J Biol Chem. 269:7030–7035. 1994.
37	Clerk A, Fuller SJ, Michael A, et al: Stimulation of ‘stressregulated’ mitogen-activated protein kinases (stress-activated protein kinases/c-Jun N-terminal kinases and p38-mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses. J Biol Chem. 273:7228–7234. 1998.
38	Shim HY, Park JH, Paik HD, et al: Acacetin-induced apoptosis of human breast cancer MCF-7 cells involves caspase cascade, mitochondria-mediated death signaling and SAPK/JNK1/2-c-Jun activation. Mol Cell. 24:95–104. 2007.PubMed/NCBI
39	Verma M, Singh SK, Bhushan S, et al: Induction of mitochondrial-dependent apoptosis by an essential oil from Tanacetum gracile. Planta Med. 74:515–520. 2008. View Article : Google Scholar : PubMed/NCBI
40	Matsuo AL, Figueiredo CR, Arruda DC, et al: α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model. Biochem Biophys Res Commun. 411:449–454. 2011.