Cleistanthin B causes G1 arrest and induces apoptosis in mammalian cells

被引:0
作者
Pradheep Kumar C.P. [1 ,3 ]
Pande G. [2 ]
Shanmugam G. [1 ,3 ]
机构
[1] Cancer Biology Division, School of Biological Sciences, Madurai Kamaraj University
[2] Ctr. for Cell. and Molecular Biology, Uppal Road
[3] School of Biological Sciences, Madurai Kamaraj University
关键词
Apoptosis; Cell cycle; Cleistanthin B; Etoposide;
D O I
10.1023/A:1009658518998
中图分类号
学科分类号
摘要
Cleistanthin B is a potential anticancer agent isolated from the tropical plant Cleistanthus collinus. We have previously shown that cleistanthin B is clastogenic and induces micronuclei formation and chromosomal aberrations.1 We now show that this compound inhibits DNA synthesis in Chinese hamster ovary (CHO) cells and induces apoptosis in cervical carcinoma (SiHa) cells. Flow cytometric analysis of cleistanthin treated CHO cells revealed that they were blocked in G1. Cervical carcinoma (SiHa) cells exposed to cleistanthin B shrank, rounded up and had condensed chromatin and fragmented nuclei. DNA isolated from cleistanthin treated cells exhibited the characteristic apoptotic ladder when electrophoresed in agarose gels. These results were confirmed by flow cytometry. Etoposide, a structurally similar compound also induced apoptosis in these cells although with a difference. Etoposide induced apoptosis after permitting cells to enter into S phase, while cleistanthin B stopped entry of cells into S phase and subsequently drove them to apoptosis.
引用
收藏
页码:413 / 419
页数:6
相关论文
共 17 条
[1]  
Pradheep Kumar, C.P., Panneerselvam, N., Rajesh, S., Shanmugam, G., Cytotoxic and genotoxic effects of cleistanthin B in normal and tumour cells (1996) Mutagenesis, 11, pp. 543-547
[2]  
Bhakuni, D.S., Dhar, M.L., Dhar, M.M., Dhawan, B.N., Mehrota, B.N., Screening of Indian plants for biological activity part II (1969) Indian Exp Bio, 7, p. 20
[3]  
Pradheepkumar, C.P., (1998) Regulation of Cell Proliferation: Effects of Cleistanthins on the Proliferation of Normal and Tumour Cells, , Ph D Thesis. Madurai Kamaraj University
[4]  
Kerr, J.F.R., Wyllie, A.H., Currie, A.R., Apoptosis: A basic biological phenomenon with wide-ranging implication in disease kinetics (1972) Br J Cancer, 26, pp. 239-257
[5]  
Sen, S., D'Incalci, M., Apoptosis: Biological events and relevance to cancer chemotherapy (1992) FEBS Lett, 307, pp. 122-127
[6]  
Fawthrop, D.J., Boobis, A.R., Davies, D.S., Mechanisms of cell death (1991) Arch Toxicol, 65, pp. 437-444
[7]  
Barry, M.A., Behnke, C.A., Eastman, A., Activation of programmed cell death (Apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia (1990) Biochem Pharmacol, 40, pp. 2353-2362
[8]  
Ormerod, M.G., Orr, R.M., Peacock, J.H., The role of apoptosis in cell killing by cisplatin: A flow cytometric study (1994) Br J Cancer, 69, pp. 93-100
[9]  
Kastan, M.B., Zhan, Q., El-Diery, W.S., A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia (1992) Cell, 71, pp. 587-597
[10]  
Waldman, T., Lengauer, C., Kinzler, K.W., Vogelstein, B., Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking P21 (1996) Nature, 381, pp. 713-716