Doxorubicin-induced apoptosis

Green PS, Leeuwenburgh C (2002) Mitochondrial dysfunction is an early indicator of doxorubicin-induced apoptosis. Biochimica et Biophysica Acta-Molecular Basis of Disease 1588 94-101. 

Wang S, Konorev EA, Kotamraju S, et al. Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms, intermediacy of H(2) 0(2)- and p53-dependent pathways. J Biol Chem. 2004 279 25535-25543. 

Wu et al. (1998) noted that doxorubicin-induced apoptosis in lymphoid cells was blocked by pepstatin A, which is an inhibitor of cathepsin D. These investigators also observed that cathepsin D was induced through p53 DNA-binding sites at the cathepsin D promoter. Moreover, they have found that, compared to fibroblasts from wild-type mice, cathepsin D-/- fibroblasts from gene knock-out mice exhibited increased resistance to death caused by doxorubicin. Also, in serum-deprived rat PC 12 cells undergoing apoptosis, the amount of cathepsin B has been observed to decline, while the level of cathepsin D increased (Shibata et al, 1998), and, in our laboratory (Kagedal et al., 2001), the same phenomenon was recently seen in human fibroblasts exposed to naphthazarin. 

Cuvillier, O., Nava, V.E., Murthy, S.K., Edsall, L.C., Levade, T., Milstien, S. and Spiegel, S., 2001, Sphingosine generation, cytochrome c release, and activation ofcaspase-7 in doxorubicin-induced apoptosis of MCF7 breast adenocarcinoma cells, Cell Death Differ 8 162-171. 

Andrieu-Abadie N, Jaffrezou JP, Hatem S, Laurent G, Levade T, Mercadier JJ. L-Carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes role of inhibition of ceramide generation. 125. FASEB J. 1999 13 1501-1510. 

Doxorubicin is an anthracychne antibiotic. Cells treated with doxorubicin have been shown to manifest the characteristic morphologic changes associated with apoptosis or programmed cell death. Doxorubicin-induced apoptosis may be an integral component of the cellular mechanism of action relating to therapeutic effects, toxicities, or both. 

Ramachandran, C., You, W., and Krishan, A., Bcl-2 and mdr-1 gene expression during doxorubicin-induced apoptosis in murine leukemic p388 and p388/R84 c Ws, Anticancer Res.,... 

Malugin A, Kopeckova P, Kopecek J. HPMA copolymer-bound doxorubicin induces apoptosis in human ovarian cancer cells by a Fas-independent pathway. J Cont Rel 2003 91 254. 

Doxorubicin treatment induced disruption of inner mitochondrial membrane potential Atjin, that precedes the nuclear signs of apoptosis (Decaudin et al. 1997). Both loss of At ini and apoptosis were prevented by Bcl-2 overexpression (Antoku et al. 1997, Decaudin et al. 1997), suggesting an important role for mitochondria in doxorubicin-induced apoptosis. Western blot analysis of Jurkat cell extracts indicated that caspases 2,3,4,6,7,8,9, and 10 were activated by doxorubicin (Gamen et al. 2000). Doxorubicin cytotoxicity was blocked by the protein synthesis inhibitor cycloheximide. 

Frias MA, Lang U, Gerber-Wicht C, James RW. Native and reconstituted HDL protect cardiomyo-cytes from doxorubicin-induced apoptosis. Cardiovasc Res 85 118-126. 

K4. Konopleva, M., Tari, A., Lopez-Berestein, A., and Andreeff, M., Inhibition of Bcl-2 with liposomal-derived antisense oligonucleotides (AS-ODN) induces apoptosis and increases the sensitivity of primary acute myeloid leukemia (AML) cells and cell lines to cytosine arabi-noside and doxorubicin. Blood 90 (suppl. 1), 10494a (1997). 

Black cohosh 2. Caffeine 3. Evening primrose oil 4. Scutellaria baicalensis 5. Starflower (borage) 1. Docetaxel 2. Paditaxel 3. Doxorubicin 4. Tamoxifen 5. Cisplatin 6. Vinorelbine t cytotoxic properties Unknown mechanism (black cohosh). Caffeine t cytotoxic effects of cisplatin wogonin present in Scutellaria enhances etoposide-induced apoptosis. Gamolenic acid found in evening primrose oil and borage potentiated the in vitro toxicity of paditaxel and vinorelbine, attributed to an unsaturated fatty acid as modulators of tumour cell chemosensitivity Be aware and avoid concomitant use... 

Neville-Webbe, H.L., Rostami-Hodjegan, A., Evans, C.A., Coleman, R.E., and Holen, I. (2005). Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer 113 364-371. 

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