Drug-induced apoptosis

Dassonneville L, Lansiaux A, Wattez N, et al. Cytotoxicity and cell cycle effects of the plant alkaloids cryptolepine and neocryptolepine relation to drug-induced apoptosis. J Nat Prod 2001 64 134-135. 

Figure 1. Ceramide mediated apoptosis signaling, Recent investigations hypothesize that, at least for drug induced apoptosis, the src kinase Lyn is activated and recruited to plasma membrane rafts. There it binds to and activates a neutral sphingomyelinase (SMase) within minutes. This initial rise in ceramide levels initiates an apoptotic cascade. Howevo- several cellular events can inhibit ceramide production (by blocking sphingomyelinase activation or clearing out ceramide accumulation through increased metabolisation) and therefore contribute to cellular resistance/survival.

Grant S, Jarvis DW (1996) Modulation of drug-induced apoptosis by interruption of protein kinase C signal transduction pathway a new therapeutic strategy. Clin Cancer Res 2 1915-1920... 

Jamieson L, Carpenter L, Biden TJ, Fields AP (1999) Protein kinase Ci activity is necessary for Bcr-Abl-mediated resistance to drug-induced apoptosis. ) Biol Chem 274 3927-3930... 

Murray NR, Fields AP (1997) Atypical protein kinase C i protects human leukemia cells against drug-induced apoptosis.) Biol Chem 272 27521-27524 Murray NR, Thompson LJ, Fields AP (1997) The role of protein kinase C in cellular proliferation and cell cycle control. In Molecular Biology Intelligence Unit Protein Kinase C, PJ Parker and LV Dekker (eds.), R.G. Landes Company, Austin, TX, Springer-Verlag, Heidelberg, 97-120... 

Yamazaki R., Kusunoki N., Matsuzaki T., Hashimoto S., and Kawai S. (2002). Nonsteroidal antiinflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor y in rheumatoid synovial cells. J. Pharmacol. Exp. Ther. 302 18-25. 

Shureiqi, I., Chen, D., Lee, J.J. et al., Lippman S.M., 15-LOX-l a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells, J. Natl Cancer Inst., 92, 1136, 2000. 

Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels, Cell Death and Differentiation 7 574-586. 

In the literature, most drug-induced apoptosis is well known to require intracellular hyper-production of reactive oxygen species and several antioxidants inhibit apoptotic cell death. While it is clear that peroxidation reactions induce apoptosis, the precise molecular mechanism of how reactive oxygen species convey death-signals is unknown. 

However it was later shown that fumonisin B1 treatment does not impair receptor- or drug-induced apoptosis (Jaffrezou et al., 1996), strenghtening the notion that sphingomyelin breakdown plays the major part in the generation of the biologically relevant ceramide. 

Fulda S, et al. Smac agonists sensitize for Apo2I7TRAIL- or 123. anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo. Nat. Med. 2002 8 808-815. 

Tsutsumi S, Gotoh T, Tomisato W, Mima S, Hoshino T, Hwang HJ, Takenaka H, Tsuchiya T, Mori M, Mizushima T. Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis. Cell Death Differ. 

Walker, P. R., Smith, C., Youdale, T., Leblanc, J., Whitfield, J. F and Sikorska, M. (1991) Topoisomerase Il-reactive chemotherapeutic drugs induce apoptosis in thymocytes. Cancer Res. 51,1078-1085. 

Shureiqi I, Chen D, Lotan R, Yang P, Newman RA, Fischer SM, Lippman SM. 15-Lipox-ygenase-1 mediates nonsteroidal anti-inflammatory drug-induced apoptosis independently of cyclooxygenase-2 in colon cancer cells. Cancer Res. 60 (2000) 6846-6850. 

Importantly, in a recent study, overexpression of SKI is linked to the upregulation of Bcr-Abl, leading to alterations of the balance between pro-apoptotic Ci8-ceramide and pro-survival SIP, leading to resistance to imatinib mesylate in K562 human CML cells (Baran et al., 2007). Importantly, down-regulation of SKI significantly reversed resistance to drug-induced apoptosis in these cells (Baran et al., 2007). 

MacKeigan, J. P., Clements, C. M., Lich, J. D., Pope, R. M., Hod, Y, Sc Ting, J. P. (2003). Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma Identification of RS/DJ-1 and RhoGDIalpha. Cancer Research, 63, 6928-6934. 

The glucocorticoids have been found not only to increase apoptosis, but also to modulate the expression of apoptosis-related markers in both unstimulated and IL-2-stimulated T lymphocytes. In one study, this class of drugs induced apoptosis while reducing Bcl-2, Fas, and CD25 expression. Only negligible effects were detected on Bax expression, a fact which points towards a potential mechanism by which some corticoids exert their anti-inflammatory effects [59]. 

Lindenboim, L., Haviv, R. and Stein, R. (1995) Inhibition of drug-induced apoptosis by survival factors in PC12 cells. J. Neurochem. 64 1054-1063. 

Friesen, C., Herr, I., Krammer, P.H. and Debatin, K.-M. (1996) Involvement of the CD95 (Apo-l/Fas) receptor/Ugand system in drug-induced apoptosis in leukemia cells. Nat. Med. 2 574-577. 

Fulda S, Kufer MU, Meyer F et al. Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene 2001 20 5865-5877. 

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