Biological evaluation of 8-alkyl xanthines as potential cytotoxic agents

Abstract

A series of 8-substituted alkyl xanthines were evaluated in vitro to test the cytotoxocity in cells. For this experiment, we utilized different mammalian cancer cell lines primarily representing prostrate and lung. One of the compounds synthesized, viz. 8-tertbutyl caffeine showed potent anticancer activity at low concentrations against DU145 when compared to adriamycin. Further experiments were carried out to check the cell cycle arrest in the DU145 cells treated with adriamycin, caffeine and 8-tert butyl caffeine. We observed that there was an arrest in G1 phase of cell cycle at 24 hours while at 48 hours of incubation, the cells were constantly distributed (59.71% -70.79%). We conclude that the effect of 8-tertbutyl caffeine is relatively comparable to caffeine whereas in adriamycin treated cells, we observed the cells underwent G2 arrest. We evaluate the studies on these effects by showing potent analogues which could be used as promising anticancer agents.

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Suravajhala, R. , Suri, N. , Bhagat, M. and Saxena, A. (2013) Biological evaluation of 8-alkyl xanthines as potential cytotoxic agents. Advances in Biological Chemistry, 3, 314-319. doi: 10.4236/abc.2013.33035.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Tenzer, A. and Pruschy, M. (2003) Potentiation of DNAdamage-induced cytotoxicity by G2checkpoint abrogators. Current Medicinal Chemistry—Anti-Cancer Agents, 3, 35-46. doi:10.2174/1568011033353533
[2] Lehman, T.A., Bennett, W.P., Metcalf, R.A., Welsh, J.A., Ecker, J., Modali, R.V., Ullrich, S., Romano, J.W., Appella, E. and Testa, J.R. (1991) p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Research, 51, 40904096.
[3] Kastan, M.B., Onyekwere, O., Sidransky, D., Vogelstein, B. and Craig, R.W. (1991) Participation of p53 protein in the cellular response to DNA damage. Cancer Research, 51, 6304-6311
[4] Lee, J.M. and Bernstein, A. (1995) Apoptosis, cancer and the p53 tumour suppressor gene. Cancer and Metastasis Reviews, 14, 149-161. doi:10.1007/BF00665797
[5] Serafin, A.M., Akudugu, J.M. and Böhm, L. (2003) Studies on the influence of DNA repair on radio-sensitivity in prostate cell lines. Urological Research, 31, 227231. doi:10.1007/s00240-003-0299-0
[6] Katsuro, T. and Hiroyuki, T. (1989) Caffeine enhancement of the effect of anticancer agents on human sarcoma cells. Cancer Science, 80, 83-88. doi:10.1111/j.1349-7006.1989.tb02249.x
[7] Saito, Y., Gopalan, B., Mhashilkar, A.M., Roth, J.A., Chada, S., Zumstein, L. and Ramesh, R. (2003) Adenovirus-mediated PTEN treatment combined with caffeine produces a synergistic therapeutic effect in colorectal cancer cells. Cancer Gene Therapy, 10, 803-813. doi:10.1038/sj.cgt.7700644
[8] Maity, A., Kao, G.D., Muschel, R.J. and McKenna, W.G. (1997) Potential molecular targets for manipulating the radiation response. International Journal of Radiation Oncology, Biology, Physics, 37, 639-653. doi:10.1016/S0360-3016(96)00598-6
[9] Zhu, W.Y. and Melera, P.W. (2001) Levels of metallothionein I and II expression in mouse embryo broblasts enhance growth in low folate through a cell cycle mediated pathway. Cell Biology, 21, 1261.
[10] Russell, K.J., Wiens, L.W., Demers, G.W., Galloway, D.A., Plon, S.E. and Groudine, M. (1995) Abrogation of the G2 checkpoint results in differential radiosensitization of G1 checkpoint-deficient and G1 checkpoint-competent cells. Cancer Research, 55, 1639-1642. doi:10.1016/0360-3016(95)97826-M
[11] Monks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Langley, J., Cronise, P. and Vaigro-Wolff, A. (1991) Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. Journal of the National Cancer Institute, 83, 757-766. doi:10.1093/jnci/83.11.757
[12] Siu, W.Y., Yam, C.H. and Poon, R.Y. (1999) G1 versus G2 cell cycle arrest after adriamycin-induced damage in mouse Swiss3T3 cells. FEBS Letters, 461, 299-305. doi:10.1016/S0014-5793(99)01481-7
[13] Bode, A.M. and Dong, Z. (2007) The enigmatic effects of caffeine in cell cycle and cancer. Cancer Letters, 247, 2639. doi:10.1016/j.canlet.2006.03.032

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