Browse > Article
http://dx.doi.org/10.5487/TR.2007.23.3.215

Requirement of Reactive Oxygen Species Generation in Apoptosis of MCF-7 Human Breast Carcinoma Cells Induced by Sanguinarine  

Lim, Ji-Young (Korea Science Academy)
Lee, Yae-Lim (Korea Science Academy)
Lee, Hae-Rin (Korea Science Academy)
Choi, Woo-Young (Department of Biology, Pusan National University)
Lee, Won-Ho (Department of Biology, Pusan National University)
Choi, Yung-Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control, Dongeui University Graduate School)
Publication Information
Toxicological Research / v.23, no.3, 2007 , pp. 215-221 More about this Journal
Abstract
Although sanguinarine, a benzophenanthridine alkaloid, possesses anti-cancer properties against several cancer cell lines, the molecular mechanisms by which it inhibits cell growth and induces apoptosis have not been clearly understood. In order to further explore the critical events leading to apoptosis in sanguinarine-treated MCF-7 human breast carcinoma cells, the following effects of sanguinarine on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 family proteins. We show that sanguinarine-induced apoptosis is accompanied by the generation of intracellular ROS and disruption of MMP as well as an increase in pro-apoptotic Bax expression and a decrease of anti-apoptotic Bcl-2 and Bcl-xL expression. The quenching of ROS generation with N-acetyl-L-cysteine, the ROS scavenger, protected the sanguinarine-elicited ROS generation, mitochondrial dysfunction, modulation of Bcl-2 family proteins, and apoptosis. Based on these results, we propose that the cellular ROS generation plays a pivotal role in the initiation of sanguinarine-triggered apoptotic death.
Keywords
Sanguinarine; Reactive oxygen species; Mitochondrial membrane potential; Apoptosis.;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Adhami, V.M., Aziz, M.H., Reagan-Shaw, S.R., Nihal, M., Mukhtar, H. and Ahmad, N. (2004). Sanguinarine causes cell cycleblockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclincyclin- dependent kinase machinery. Mol. Cancer Ther., 3, 933-940
2 Chowdhury, I., Tharakan, B. and Bhat, G.K. (2006). Current concepts in apoptosis: The physiological suicide program revisited. Cell. Mol. Biol. Lett., 11, 506-525   DOI   ScienceOn
3 Debiton, E., Madelmont, J.C., Legault, J. and Barthomeuf, C. (2003). Sanguinarine-induced apoptosis is associated with an early and severe cellular glutathione depletion. Cancer Chemother. Pharmacol., 51, 474-482
4 Hussain, A.R., Al-Jomah, N.A., Siraj, A.K., Manogaran, P., Al- Hussein, K., Abubaker, J., Platanias, L.C., Al-Kuraya, K.S. and Uddin, S. (2007). Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells. Cancer Res., 67, 3888-3897   DOI   ScienceOn
5 Thannickal, V.J. and Fanburg, B.L. (2000). Reactive oxygen species in cell signaling. Am. J. Physiol. Lung Cell. Mol. Physiol., 279, L1005-L1028
6 Weerasinghe, P., Hallock, S. and Liepins, A. (2001a). Bax, Bcl-2, and NF-$\kappa$B expression in sanguinarine-induced bimodal cell death. Exp. Mol. Pathol., 71, 89-98   DOI   ScienceOn
7 Tsujimoto, Y. and Shimizu, S. (2002). The voltage-dependent anion channel: an essential player in apoptosis. Biochimie, 84, 187-193   DOI   ScienceOn
8 Mandel, I.D. (1998). Chemotherapeutic agents for controlling plaque and gingivitis. J. Clin. Periodontol., 15, 488-498   DOI
9 Suh, Y.A., Arnold, R.S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A.B., Griendling, K.K. and Lambeth, J.D. (1999). Cell transformation by the superoxide-generating oxidase Mox1. Nature, 401, 79–82
10 Ghobrial, I.M., Witzig, T.E. and Adjei, A.A. (2005). Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin., 55, 178-194   DOI   ScienceOn
11 Weerasinghe, P., Hallock, S., Tang, S.C. and Liepins, A. (2001b). Role of Bcl-2 family proteins and caspase-3 in sanguinarine-induced bimodal cell death. Cell Biol. Toxicol., 17, 371-381   DOI
12 Ding, Z., Tang, S.C., Weerasinghe, P., Yang, X., Pater, A. and Liepins, A. (2002). The alkaloid sanguinarine is effective against multidrug resistance in human cervical cells via bimodal cell death. Biochem. Pharmacol., 63, 1415-1421   DOI   ScienceOn
13 Poppe, M., Reimertz, C., Dussmann, H., Krohn, A.J., Luetjens, C.M., Bockelmann, D., Nieminen, A.L., Kögel, D. and Prehn, J.H. (2001). Dissipation of potassium and proton gradients inhibits mitochondrial hyperpolarization and cytochrome c release during neural apoptosis. J. Neurosci., 21, 4551-4563   DOI
14 Deveraux, Q.L. and Reed, J.C. (1999). IAP family proteinssuppressors of apoptosis. Genes Dev., 13, 239-252   DOI
15 Mahady, G.B. and Beecher, C.W. (1994). Quercetin-induced benzophenanthridine alkaloid production in suspension cell cultures of Sanguinaria canadensis. Planta Med., 60, 553-557   DOI   ScienceOn
16 Cathcart, R., Schwiers, E. and Ames, B.N. (1983). Detection of picomole levels of hydroperoxides using a fluorescent dichlorofluorescein assay. Anal. Biochem., 134, 111-116   DOI   ScienceOn
17 Chang, M.C., Chan, C.P., Wang, Y.J., Lee, P.H., Chen, L.I., Tsai, Y.L., Lin, B.R., Wang, Y.L. and Jeng, H. (2007). Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization. Toxicol. Appl. Pharmacol., 218, 143-151   DOI   ScienceOn
18 Hagen, T. and Vidal-Puig, A. (2002). Mitochondrial uncoupling proteins in human physiology and disease. Minerva Med., 93, 41-57
19 Han, M.H., Kim, S.O., Kim, G.Y., Kwon, T.K., Choi, B.T., Lee, W.H. and Choi, Y.H. (2007). Induction of apoptosis by sanguinarine in C6 rat glioblastoma cells is associated with the modulation of the Bcl-2 family and activation of caspases through downregulation of extracellular signalregulated kinase and Akt. Anti-Cancer Drugs, 18, 913- 921
20 Ozben, T. (2007). Oxidative stress and apoptosis: Impact on cancer therapy. J. Pharm. Sci., 96, 2181-2196   DOI   ScienceOn
21 Adhami, V.M., Aziz, M.H., Mukhtar, H. and Ahmad, N. (2003). Activation of prodeath Bcl-2 family proteins and mitochondrial apoptosis pathway by sanguinarine in immortalized human HaCaT keratinocytes. Clin. Cancer Res., 9, 3176- 3182
22 Ahmad, N., Gupta, S., Husain, M.M., Heiskanen, K.M. and Mukhtar, H. (2000). Differential antiproliferative and apoptotic response of sanguinarine for cancer cells versus normal cells. Clin. Cancer Res., 6, 1524-1528
23 Laster, L.L. and Lobene, R.R. (1990). New perspectives on Sanguinaria clinicals: individual toothpaste and oral rinse testing. J. Can. Dent. Assoc., 56, S19-S30
24 Vavreckova, C., Gawlik, I. and Muller, K. (1996). Benzophenanthridine alkaloids of Chelidonium majus; II. Potent inhibitory action against the growth of human keratinocytes. Planta Med., 62, 491-494   DOI   ScienceOn
25 Weerasinghe, P., Hallock, S., Tang, S.C., Trump, B. and Liepins, A. (2006). Sanguinarine overcomes P-glycoprotein- mediatedmultidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells. Exp. Toxicol. Pathol., 58, 21-30   DOI   ScienceOn
26 Fulda, S. and Debatin, K.M. (2006). Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 25, 4798-4811   DOI   ScienceOn
27 Makin, G. and Dive, C. (2001). Apoptosis and cancer chemotherapy. Trends Cell Biol., 11, S22-S26   DOI   ScienceOn
28 Skulachev, V.P. (2006). Bioenergetic aspects of apoptosis, necrosis and mitoptosis. Apoptosis, 11, 473-485   DOI