Browse > Article
http://dx.doi.org/10.5352/JLS.2012.22.6.815

Induction of Apoptosis and Inhibition of NO Production by Piceatannol in Human Lung Cancer A549 Cells  

Choi, Yung-Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine, Department of Biomaterial Control (BK21 program), Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University)
Publication Information
Journal of Life Science / v.22, no.6, 2012 , pp. 815-822 More about this Journal
Abstract
Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), a natural stilbene, is an analogue of resveratrol. Although recent experimental data have revealed the health benefit potency of piceatannol, the molecular mechanisms underlying the anti-cancer activity have not yet been studied in detail. In the present study, the further possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human lung cancer A549 cells were investigated. Exposure of A549 cells to piceatannol resulted in growth inhibition and induction of apoptosis. Apoptosis induction of A549 cells by piceatannol showed correlation with proteolytic activation of caspase-3, -8, and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase, phospholipase C-${\gamma}1$, ${\beta}$-catenin, and Inhibitor caspase-activated DNase. The increase in apoptosis by piceatannol treatment was also associated with an increase of pro-apoptotic Bax expression and decrease of anti-apoptotic Bcl-2 and Bcl-xL expression, and caused down-regulation of the inhibitor of apoptosis protein family members and up-regulation of Fas and Fas legend. In addition, piceatannol treatment markedly inhibited the expression of mRNA and proteins of inducible nitric oxide (NO) synthase, and the levels of NO production were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. The results indicate that piceatannol may have therapeutic potential against human gastric cancer cells.
Keywords
Piceatannol; A549 cells; apoptosis; nitric oxide (NO);
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Ashikawa K., Majumdar, S., Banerjee, S., Bharti, A. C., Shishodia, S. and Aggarwal, B.B. 2002. Piceatannol inhibits TNF-induced NF-$\kappa B$ activation and NF-$\kappa B$-mediated gene expression through suppression of $I \kappa B\alpha$ kinase and p65 phosphorylation. J. Immunol. 169, 6490-6497.   DOI
2 Bae, S. S., Perry, D. K., Oh, Y. S., Choi, J. H., Galadari, S. H., Ghayur, T., Ryu, S. H., Hannun, Y. A. and Suh, P. G. 2000. Proteolytic cleavage of phospholipase C-gamma1 during apoptosis in Molt-4 cells. FASEB J. 14, 1083-1092.
3 Barton, B. E., Karras, J. G., Murphy, T. F., Barton, A. and Huang, H. F. 2004. Signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer: Direct STAT3 inhibition induces apoptosis in prostate cancer lines. Mol. Cancer Ther. 3, 11-20.   DOI
4 Bavaresco, L., Fregoni, C., Cantu, E. and Trevisan, M. 1999. Stilbene compounds: from the grapevine to wine. Drugs Exp. Clin. Res. 25, 57-63.
5 Berridge, M. J. and Irvine, R. F. 1984. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312, 315-321.   DOI   ScienceOn
6 Brancolini, C., Lazarevic, D., Rodriguez, J. and Schneider, C. 1997. Dismantling cell-cell contacts during apoptosis is coupled to a caspase-dependent proteolytic cleavage of $\beta$-catenin. J. Cell Biol. 139, 759-771.   DOI
7 Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A and Nagata, S. 1998. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391, 43-50.   DOI   ScienceOn
8 Ferreira, M. J., Duarte, N., Gyemant, N., Radics, R., Cherepnev, G., Varga, A. and Molnar, J. 2006. Interaction between doxorubicin and the resistance modifier stilbene on multidrug resistant mouse lymphoma and human breast cancer cells. Anticancer Res. 26, 3541-3546.
9 Ferrigni, N. R., McLaughlin, J. L., Powell, R. G. and Smith, Jr. C. R. 1984. Use of potato disc and brine shrimp bioassays to detect activity and isolate piceatannol as the antileukemic principle from the seeds of Euphorbia lagascae. J. Nat. Prod. 47, 347-352.   DOI
10 Galluzzi, L., Larochette, N., Zamzami, N. and Kroemer, G. 2006. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene 25, 4812-4830.   DOI
11 Geahlen, R. L. and McLaughlin, J. L. 1989. Piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor. Biochem. Biophys. Res. Commun. 165, 241-245.   DOI   ScienceOn
12 Ghobrial, I. M., Witzig, T. E. and Adjei, A. A. 2005. Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin. 55, 178-194.   DOI   ScienceOn
13 Han, S. I., Kim, Y. S. and Kim, T. H. 2008. Role of apoptotic and necrotic cell death under physiologic conditions. BMB Rep. 41, 1-10.   DOI
14 Hellmuth, M., Paulukat, J., Ninic, R., Pfeilschifter, J. and Mühl, H. 2004. Nitric oxide differentially regulates pro- and anti-angiogenic markers in DLD-1 colon carcinoma cells. FEBS Lett. 563, 98-102.   DOI
15 Hirst, D. G. and Robson, T. 2010. Nitrosative stress as a mediator of apoptosis: implications for cancer therapy. Curr. Pharm. Des. 16, 45-55.   DOI   ScienceOn
16 Javadov, S. and Karmazyn, M. 2007. Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection. Cell. Physiol. Biochem. 20, 1-22.   DOI
17 Jeong, S. Y. and Seol, D. W. 2008. The role of mitochondria in apoptosis. BMB Rep. 41, 11-22.   DOI
18 Jin, Z. and El-Deiry, W. S. 2005. Overview of cell death signaling pathways. Cancer Biol. Ther. 4, 139-163.   DOI   ScienceOn
19 Kaufmann, S. H., Desnoyers, S., Ottaviano, Y., Davidson, N. E. and Poirier, G. G. 1993. Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy- induced apoptosis. Cancer Res. 53, 3976-3985.
20 Kumari, A. L., Ali, A. M., Das, S., Pardhasaradhi, B. V., Varalakshmi, C. H. and Khar, A. 2005. Role of STAT3 and NF-$\kappa B$ signaling in the serum factor-induced apoptosis in AK-5 cells. Biochem. Biophys. Res. Commun. 336, 860-867.   DOI
21 Larrosa, M., Tomas-Barberan, F. A. and Espin, J. C. 2004. The grape and wine polyphenol piceatannol is a potent inducer of apoptosis in human SK-Mel-28 melanoma cells. Eur. J. Nutr. 43, 275-284.   DOI
22 Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S., Poirier, G. G. and Earnshaw, W. C. 1994. Cleavage of poly (ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371, 346-347.   DOI   ScienceOn
23 Nakamoto, K., Kuratsu, J. and Ozawa, M. 2005. $\beta$-catenin cleavage in non-apoptotic cells with reduced cell adhesion activity. Int. J. Mol. Med. 15, 973-979.
24 Nishizuka, Y. and Kikkawa, U. 2003. Early studies of protein kinase C: a historical perspective. Methods Mol. Biol. 233, 9-18.
25 Okada, H. and Mak, T. W. 2004. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer 4, 592-603.   DOI   ScienceOn
26 Pance, A. 2006. Nitric oxide and hormones in breast cancer: allies or enemies? Future Oncol. 2, 275-288.   DOI
27 Rao, C. V. 2004. Nitric oxide signaling in colon cancer chemoprevention. Mutat. Res. 555, 107-119.   DOI
28 Roupe, K., Teng, X. W., Fu, X., Meadows, G. G. and Davies, N. M. 2004. Determination of piceatannol in rat serum and liver microsomes: pharmacokinetics and phase I and II biotransformation. Biomed. Chromatogr. 18, 486-491.   DOI
29 Wesche-Soldato, D. E., Swan, R. Z., Chung, C. S. and Ayala, A. 2007. The apoptotic pathway as a therapeutic target in sepsis. Curr. Drug Targets 8, 493-500.   DOI
30 Su, L. and David, M. 2000. Distinct mechanisms of STAT phosphorylation via the interferon-${\alpha}/{\beta}$ receptor. Selective inhibition of STAT3 and STAT5 by piceatannol. J. Biol. Chem. 275, 12661-12666.   DOI   ScienceOn
31 Widłak, P. 2004. The DFF40/CAD endonuclease and its role in apoptosis. Acta Biochim. Pol. 47, 1037-1044.
32 Wieder, T., Prokop, A., Bagci, B., Essmann, F., Bernicke, D., Schulze-Osthoff, K., Dorken, B., Schmalz, H. G., Daniel, P. T. and Henze. G. 2001. Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts. Leukemia 15, 1735-1742.   DOI
33 Xu, M. H., Deng, C. S., Zhu, Y. Q. and Lin, J. 2003. Role of inducible nitric oxide synthase expression in aberrant crypt foci-adenoma-carcinoma sequence. World J. Gastroenterol. 9, 1246-1250.
34 Yang, G. Y., Taboada, S. and Liao, J. 2009. Induced nitric oxide synthase as a major player in the oncogenic transformation of inflamed tissue. Methods Mol. Biol. 512, 119-156.   DOI   ScienceOn