Abstract
The mechanism of action, leakage of cytochrome c from mitochondria into cytosol, for
the antineoplastic compound glyfoline was examined. Additionally, our current studies
revealed that glyfoline induced apoptotic changes and arrested cell cycle procession
at the G2/M phase in nasopharyngeal carcinoma (NPC). A reverse transcriptase polymerase
chain reaction (RT-PCR) showed no specific changes of apoptosis-related gene expression
(i. e., bax, ICE-α,β, bcl-2, and c-myc). However, no similar changes were detected
in fibroblasts and peripheral lymphocytes after glyfoline treatment suggesting that
glyfoline has a higher affinity for tumor cells than for normal cells.
Key words
Glycosmis citrifolia
- Rutaceae - nasopharyngeal carcinoma cell lines - glyfoline - apoptosis - cytochrome
c
References
- 1
Wu T -S, Furukawa H.
Structure of four new acridone alkaloids from Glycosmis citrifolia (Willd.) Lindle.
Heterocycles.
1982;
19
1047-51
- 2
Su T -L, Köhler B, Chou T -C, Chun M W, Watanabe K A.
Synthesis of the acridone alkaloids glyfoline and congeners. Structure-activity relationship
studies of cytotoxic acridones and biological activities of acridone derivatives.
J Med Chem.
1992;
35
2703-10
- 3 Gerzon K, Svoboda G. Acridone Alkaloids: Experimental Antitumor Activity of Acronycine.
In: The Alkaloids. Vol. 32 Academic Press New York; 1983: pp 1-28
- 4 Su T -L, Watanabe K A. Anticancer acridone alkaloids. In: Rahman A, Basha FZ, editors
Studies in Natural Products Chemistry: Vol. 13, Bioactive Natural Products Part (A). Elsevier Amsterdam; 1993: pp 347-82
- 5
Su T -L, Lin C -T, Chen C -H, Lin M -T.
Synthesis and antitumor evaluation of water-soluble derivatives of glyfoline.
Med Chem Res.
2000;
10
137-48
- 6
Gout P W, Dunn B P, Beer C T.
Effects of acronycine on nucleic acid synthesis and population growth in mammalian
tumor cultures.
J Cell Phys.
1971;
78
127-38
- 7
Kennedy B.
Nucleoside uptake, acronycine action and membrane fluidity during lymphocyte activation.
Biochem Soc Trans.
1979;
7
1002-3
- 8
Su T -L, Lin C -T, Chen C -H, Huang H -M.
Synthesis of biotinylated glyfoline for immunoelectron microscopic localization.
Bioconjugate Chem.
2000;
11
278-81
- 9
Lin C T, Wong C I, Chan W Y, Tzung K W, Ho J KC, Hsu M M, Chung S M.
Establishment and characterization of two nasorpharyngeal carcinoma cell lines.
Lab Invest.
1990;
62
713-24
- 10
Lin C T, Chan W Y, Chen W, Huang H M, Wu H C, Hsu M M, Chuang S M, Wang C C.
Characterization of seven newly established nasopharyngeal carcinoma cell lines.
Lab Invest.
1993;
68
716-27
- 11
Mosmann T.
Rapid colorimetric assay for cellular growth and survival. Application to proliferation
and cytotoxicity assays.
J Immunol Meth.
1983;
65
55-63
- 12
Wu H C, Lin Y J, Lee J J, Liu Y J, Liang S T, Peng Y, Chiu Y W, Wu C W, Lin C T.
Functional analysis of Epstein-Barr virus in nasopharyngeal carcinoma cell.
Lab Invest.
2003;
83
797-812
- 13
Wu H C, Huang P H, Chiu C Y, Lin C T.
G-proteinβ2 subunit antisense of oligonucleotide inhibits cell proliferation and disorganizes
microtubule and mitotic spindle organization.
J Cell Biochem.
2001;
83
136-46
- 14
Wang A M, Doyle M V, and Mark D F.
Quantitation of mRNA by the polymerase chain reaction.
Proc Nat Acad Sci USA.
1989;
86
9717-21
- 15
Agullar-Santelises M, Rottenberg M E, Lewin N, Mellstedt H, and Jondal M.
Bcl-2, Bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression.
Int J Cancer.
1996;
69
114-9
- 16
Liu X, Kim C N, Yang J, Jemmerson R, Wang X.
Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome
c.
Cell.
1994;
86
147-57
- 17
Allen R T, Cluck M W, Agrawal D K.
Mechanisms controlling cellular suicide: role of Bcl-2 and caspases.
Cell Mol Life Sci.
1998;
54
427-45
- 18
Cecconi F, Alvarez-Bolado G, Meyer B I, Roth K A, Gruss P.
Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development.
Cell.
1998;
94
727-37
- 19
Kroemer G, Dallaporta B, Resche-Rigon M.
The mitochondria death/life regulator in apoptosis and necrosis.
Ann Rev Physiol.
1998;
60
619-42
Tsann-Long Su
Institute of Biomedical Sciences
Academia Sinica
Taipei 115
Taiwan
Republic of China
Telefon: +886-2-2789-9045
Fax: +886-2-782-9142
eMail: tlsu@ibms.sinica.edu.tw