Farnesyl caffeate, synthesis of
propolis and polar bud excretion, has been reported to exhibit anti-allergic
effects in mice. However,
little is known about anti-tumor effects. In this study, we investigated the
effect of Farnesyl caffeate in cell proliferation of lung carcinoma cell line
(H157). Antiproliferative effect and apoptosis on H157 cell were evaluated
using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT)
and DNA fragmentation assay, respectively. Farnesyl caffeate inhibited the growth
of H157 cell in dose-dependent manner. Morphological changes of nuclei by
staining Hoechst 33258 and DNA fragmentation suggested that Farnesyl caffeate
induced death involved in a mechanism of apoptosis. Moreover, caspase-3,
caspase-7 and caspase-9 were activated by Farnesyl caffeate on H157 cell. The
protein expressions of Bax and Bcl-2 were down-regulated by Farnesyl caffeate,
resulting in cytochrome c release
from the mitochondria. Farnesyl caffeate significantly increased the expression
of p53 proteins which indicates that p53 plays a pivotal role in the initiation phase of
Farnesyl caffeate-induced HepG2 cell apoptosis. These results demonstrated
Farnesyl caffeate-induced apoptosis in human lung carcinoma cell line. More
detailed mechanism of Farnesyl caffeate-induced H157
apoptosis remains to be elucidated.
References
[1]
E. L. Ghisalberti, “Propolis: A Review,” BEE World, Vol. 60, No. 2, 1979, pp. 59-84.
[2]
W. Greenaway, et al., “The Analysis of Bud Exudates of Populus Euramericana and of Propolis by Gaschromatograph-Mass Spectrometry,” Proceedings of the Royal Society of London, Vol. 232, 1987, pp. 249-272. http://dx.doi.org/10.1098/rspb.1987.0073
[3]
E. M. Schneidewind, et al., “Zur Kenntnis der Inhaltsstoffe von Propolis,” Pharmazie, Vol. 30, 1975, p. 803.
[4]
E. Wollenweber, “Flavonoidmuster als Systematisches Merkmal in der Gattung Populus,” Biochemical Systematics and Ecology, Vol. 3, No. 1, 1975, pp. 35-45. http://dx.doi.org/10.1016/0305-1978(75)90039-3
[5]
M. Vanhaelen, “Propolis: Origin, Microscopic Investigations, Chemical Constituents and Therapeutical Activity,” Journal de Pharmacie de Belgique, Vol. 34, 1979, pp. 253-259.
[6]
E. Wollenweber, et al., “A Novel Caffeic Acid Derivate and Other Constitutents of Propolis Bud Excretion and Propolis (Bee-Glue),” Zeitschrift für Naturforschung, Vol. 42, 1987, pp. 1030-1034.
[7]
E. Schneidewind, et al., “Identigizierung Eines aus Propolis Isolierten Antimirobiell Wirksamen Inhaltsstoffes,” Pharmazie, Vol. 34, No. 2, 1979, pp. 103-106.
[8]
B. M. Hausen, et al., “Propolis Allergy I. Origin, Properties Usage and Literature Review,” Contact Dermatitis, Vol. 17, No. 3, 1987, pp. 163-170. http://dx.doi.org/10.1111/j.1600-0536.1987.tb02699.x
[9]
P. A. Hill, et al., “Multiple Extracellular Signals Promote Osteoblast Survival and Apoptosis,” Endocrinology, Vol. 138, No. 9, 1997, pp. 3849-3858. http://dx.doi.org/10.1210/en.138.9.3849
[10]
N. Kawazoe, et al., “Tiam1 Is Involved in the Regulation of Bufalin-Induced Apoptosis in Human Leukemia Cells,” Oncogene, Vol. 18, No. 15, 1999, pp. 2413-2421. http://dx.doi.org/10.1038/sj.onc.1202555
[11]
S. Mizukami, et al., “Imaging of Caspase-3 Activation in HeLa Cells Stimulated with Etoposide Using a Novel Fluorescent Probe,” FEBS Letters, Vol. 453, No. 3, 1999, pp. 356-360. http://dx.doi.org/10.1016/S0014-5793(99)00755-3
[12]
G. M. Cohen, “Caspase: The Executioners of Apoptosis,” Biochemical Journal, Vol. 326, No. 5693, 1997, pp. 1-16.
[13]
S. Nagata, “Apoptosis by Death Factor,” Cell, Vol. 88, No. 3, 1997, pp. 355-365. http://dx.doi.org/10.1016/S0092-8674(00)81874-7
[14]
G. R. Green and J. C. Reed, “Mitochondria and Apoptosis,” Science, Vol. 281, No. 5381, 1998, pp. 1309-1312. http://dx.doi.org/10.1126/science.281.5381.1309
[15]
L. Y. Li, X. Luo and X. Wang, “Endonuclease G Is an Apoptotic DNase When Released from Mitochondria,” Nature, Vol. 412, No. 6842, 2001, pp. 95-99. http://dx.doi.org/10.1038/35083620
[16]
J. Klefstrom, et al., “c-Myc Augments the Apoptotic Activity of Cytosolic Death Receptor Signaling Proteins by Engaging the Mitochondrial Apoptotic Pathway,” The Journal of Biological Chemistry, Vol. 277, No. 45, 2002, pp. 43224-43232. http://dx.doi.org/10.1074/jbc.M206967200
[17]
T. Hashimoto, et al., “Synthesis of Two Allergenic Constituents of Propolis and Poplar Bud Excretion,” Zeitschrift für Naturforschung, Vol. 43, No. 5-6, 1998, pp. 470-472.
[18]
M. Zhao, et al., “The Course of Uncarinic Acid-E-Induced Apoptosis of HepG2 Cells from Damage to DNA and p53 Activation to Mitochondrial Release of Cytochrome c,” Biological & Pharmaceutical Bulletin, Vol. 29, No. 8, 2006, pp. 1639-1644. http://dx.doi.org/10.1248/bpb.29.1639
[19]
S. H. Kaufmann, et al., “Specific Proteolytic Cleavage of Poly (ADP-Ribose) Polymerase: An Early Marker of Chemotherapy-Induced Apoptosis,” Cancer Research, Vol. 53, No. 17, 1993, pp. 3976-3985.
[20]
Y. K. Park, et al., “Antimicrobial Activity of Propolis on Oral Microorganisms,” Current Microbiology, Vol. 36, No. 1, 1998, pp. 24-28. http://dx.doi.org/10.1007/s002849900274
[21]
X. M. Yin, et al., “BH1 and BH2 Domains of Bcl-2 Are Required for Inhibition of Apoptosis and Heterodimerization with Bax,” Nature, Vol. 369, No. 6478, 1994, pp. 321-323. http://dx.doi.org/10.1038/369321a0
[22]
E. H. Cheng, et al., “Bax-Independent Inhibition of Apoptosis by Bcl-XL,” Nature, Vol. 379, No. 6565, 1996, pp. 554-556. http://dx.doi.org/10.1038/379554a0
[23]
J. C. Reed, “Double Identity for Proteins of the Bcl-2 Family,” Nature, Vol. 387, No. 6635, 1997, pp. 773-776. http://dx.doi.org/10.1038/42867
[24]
L. M. Adams and S. Cory, “The Bcl-2 Protein Family Arbiters of Cells Survival,” Science, Vol. 281, No. 5381, 1998, pp. 1322-1326. http://dx.doi.org/10.1126/science.281.5381.1322
[25]
D. G. Kirsch, et al., “Caspase-3-Dependent Cleavage of Bcl-2 Promotes Release of Cytochrom c,” The Journal of Biological Chemistry, Vol. 274, No. 30, 1999, pp. 21155-21161. http://dx.doi.org/10.1074/jbc.274.30.21155
[26]
R. M. Kluck, et al., “The Release of Cytochrome c from Mitochondria: A Rimary Site for Bcl-2 Regulation of Apoptosis,” Science, Vol. 275, No. 5303, 1997, pp. 1132-1136. http://dx.doi.org/10.1126/science.275.5303.1132
[27]
J. Yang, et al., “Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked,” Science, Vol. 275, No. 5303, 1997, pp. 1129-1132. http://dx.doi.org/10.1126/science.275.5303.1129
[28]
N. S. Wang, et al., “Transient Expression of Wild-Type or Mitochondrially Targeted Bcl-2 Induces Apoptosis, Whereas Transient Expression of Endoplasmic Reticulum-Targeted Bcl-2 Is Protective against Bax-Induced Cell Death,” The Journal of Biological Chemistry, Vol. 276, No. 47, 2001, pp. 44117-44128. http://dx.doi.org/10.1074/jbc.M101958200
