- Research Article
Can CYP1A1 siRNA be an effective treatment for lung cancer?
Cellular & Molecular Biology Letters volume 13, pages 240–249 (2008)
Abstract: Previously, we identified a novel correlation between the upregulated expression of telomerase (hTERT) and cytochrome P450 1A1 (CYP1A1) in A549 human lung cancer cell line. The expression correlation was confirmed by silencing CYP1A1 expression using siRNA technology and observing a silencing of hTERT transcription. Furthermore, silencing CYP1A1 and subsequently downregulating hTERT resulted in the reduction of cancer cell viability by more than 40%, which appeared as early as 24 hours after the treatment. The concomitant downregulation of CYP1A1 and hTERT resulted in rapid cell death. This finding can be further exploited to develop new molecular targets for the treatment of lung cancer.
aryl hydrocarbon receptor
- CYP1A1 :
cytochrome P450 1A1
- hTERT :
Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Klaus, W. and Tuschl, T. Duplexes of 21-nucleotide RNAs mediate RNA interference in mammalian cell culture. Nature 411 (2001a) 494–498.
Hannon, G.J. and Rossi, J.J. Unlocking the potential of the human genome with RNA interference. Nature 8S (2004) 431–371.
Wilda, M., Fuchs, U., Wossmann, W. and Borkhardt, A. Killing of leukemic cells with a BCR/ABL fusion gene by RNA interference (RNAi). Oncogene 37 (2002) 5716–5724.
Shammas, M.A., Koley, H., Batchu, R.B., Berheau, R.C., Protopopov, A., Muncshi, N.C. and Goyal, R.J. Telomerase inhibition by siRNA causes senescene and apoptosis in Barretłs adenocarcinoma cells: mechanism and therapeutic potential. Mol. Cancer 4 (2005) 1–14.
Flynn, M.A., Casey, D.G., Todryk, S.M. and Mohon, B.P. Efficient delivery of small interfering RNA for inhibition of IL-12p40 expression in vivo. J. Inflammation 1 (2004) 1–12.
Shervington, A., Mohammed, K., Patel, R. and Lea, R. Identification of a novel co-transcription of P450/1A1 with telomerase in A549. Gene 388 (2007) 100–117.
Guigal, N., Seree, E., Bourgarel-Rey, V. and Barra, Y. Induction of CYP1A1 by serum independent of AhR pathway. Biochem. Biophys. Res. Commun. 267 (2000) 572–576.
Iba, M.M., Scholl, H., Fung, J., Thomas, P.E. and Alan, J. Induction of pulmonary CYP1A1 by nicotine. Xenobiotica 28 (1995) 827–843
Guengerich, F.P. Forging the links between metabolism and carcinogenesis. Mutat. Res. 488 (2001a) 195–209.
Guengerich, F.P. Metabolism of chemical carcinogens. Carcinogenesis 21 (2000) 345–351.
Jean-Charles, S., Moon, C., Wang, L., Hittelman, W., Jang, S., Sun, S., Lee, J., Liu, D., Kurie, J., Morice, R., Lee, J., Hong, W. and Mao, L. Effects of N-(4-Hydroxyphenyl)retinamide on hTERT expression in the bronchial epithelium of cigarette smokers. J. Natl. Cancer Inst. 93 (2001) 1257–1263.
Hiyama, K. and Hiyama, E. Detection of telomerase activity in lung cancer tissues. Methods Mol. Med. 74 (2003) 401–412.
Xinarianos, G. Telomerase activity in non-small cell lung carcinomas correlates with smoking status. Int. J. Oncol. 15 (1999) 961–965.
Albanell, J., Lonardo, F., Rusch, V., Engelhardt, M., Langenfeld, J., Han, W., Klimstra, D., Venkatraman, E., Moore, M.A. and Dmitrovsky, E. High telomerase activity in primary lung cancers: association with increased cell proliferation rates and advanced pathologic stage. J. Natl. Cancer Inst. 89 (1997) 1609–1615.
Chi, J., Chang, N.Y., Wang, N.N., Chang, D.S., Dunphy, N. and Brown, P.O. Genome wide view of gene silencing by small interfering RNAs. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 6343–3646.
Ambion Inc. siRNA Target Finder. http://www.ambion.com/techlib/misc/siRNA.
Lekas, P., Tin K,L., Lee, C. and Prokipcak, R.D. The human cytochrome P450 1A1 mRNA is rapidly degraded in HepG2 cells. Arch. Biochem. Biophys. 3849 (2000) 311–318.
Nemoto, N. and Sakural, J. Increase of CYP1A1 mRNA and AHH activity by inhibitors of either protein or RNA synthesis in mouse hepatocytes in primary culture. Carcinogenesis 12 (1991) 2115–2121.
Harley, G.B., Futcher, A.B. and Greidea, C.W. Telomerase shorten during aging of human fibroblast. Nature 345 (1990) 458–460.
Shay, J.W. and Roninson, J.B. Hallmarks of senescence in carcinogensis and cancer therapy. Oncogene 12 (2004) 2919–2933.
Hukkanen, J., Lassila, A., Paivarinta, K., Valanne, S. and Sarpo, S. Induction and regulation of xenobiotic-metabolizing cytochrome P450s in the human A549 lung adenocarcinoma cell line. Am. J. Respir. Cell Mol. Biol. 22 (2000) 360–366.
Liu, W., Zhang, Y., Shen, Y., Jiang, J., Miao, Z. and Ding, J. Telomerase inhibition is a specific early event in salvicine-treated human lung adenocarcinoma A549 cells. Biochem. Biophys. Res. Commun. 323 (2004) 660–667.
Rossi, M.J. Inhibition of telomerase activity by ceramide in A549 human lung adenocarcinoma cells. Mol. Med. J. 2000 (2000) 1–5.
Pratt, W. and Toft, D. Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp. Biol. Med. 228 (2004) 111–133.
Carver, L.A., Jackiw, V. and Bradfield, C.A. The 90-kDa heat shock protein is essential for Ah receptor signaling in a yeast expression system. J. Biol. Chem. 269 (1994) 30109–30112.
Holt, S.E., Aisner, D.L., Baur, J., Tesmer, V.M. and Dy, D. Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev. 13 (1999) 817–826.
Chang, S. and DePinho, R.A. Telomerase extracurricular activities. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 12520–12522.
About this article
Cite this article
Mohammed, K., Shervington, A. Can CYP1A1 siRNA be an effective treatment for lung cancer?. Cell Mol Biol Lett 13, 240–249 (2008). https://doi.org/10.2478/s11658-007-0050-x
- gene knockdown