American Association for Cancer Research

Table 1

Paclitaxel and docetaxel stimulate doxorubicin and doxorubicin aglycone metabolism by dialysis-inhibitable interactions with human cardiac reductases

Cytosol (0.3 mg prot./ml) was incubated for 1 h with 1 μm taxanes or equivalent volume of taxane-free ethanol in 0.3 m NaCl (pH 7.0) at 4°C. Subsequently, cytosol was dialyzed overnight against 0.3 m NaCl (pH 7.0) at 4°C and eventually reconstituted with 100 μm NADPH and 25 μm doxorubicin or doxorubicinol aglycone to assess the formation of doxorubicinol or doxorubicinol aglycone, respectively. Where indicated, 1 μm paclitaxel or docetaxel was reintroduced in the incubations containing dialyzed cytosol, NADPH, and the anthracycline. Values are taken from representative experiments in a cytosol that metabolized doxorubicin or doxorubicin aglycone with basal activities of 0.33 nmol doxorubicinol/mg protein/4 h or 0.73 nmol doxorubicinol aglycone/mg prot./4 h, respectively.
	Doxorubicinol	Doxorubicinol aglycone
Experimental condition	(nmol/mg protein/4 h)
Ethanol → Dialysis	0.35	0.69
Paclitaxel → Dialysis	0.39	0.71
Docetaxel → Dialysis	0.32	0.60
Paclitaxel → Dialysis + Paclitaxel	0.59	1.1
Docetaxel → Dialysis + Docetaxel	0.62	1.2

Cytosol (0.3 mg prot./ml) was incubated for 1 h with 1 μm taxanes or equivalent volume of taxane-free ethanol in 0.3 m NaCl (pH 7.0) at 4°C. Subsequently, cytosol was dialyzed overnight against 0.3 m NaCl (pH 7.0) at 4°C and eventually reconstituted with 100 μm NADPH and 25 μm doxorubicin or doxorubicinol aglycone to assess the formation of doxorubicinol or doxorubicinol aglycone, respectively. Where indicated, 1 μm paclitaxel or docetaxel was reintroduced in the incubations containing dialyzed cytosol, NADPH, and the anthracycline. Values are taken from representative experiments in a cytosol that metabolized doxorubicin or doxorubicin aglycone with basal activities of 0.33 nmol doxorubicinol/mg protein/4 h or 0.73 nmol doxorubicinol aglycone/mg prot./4 h, respectively.
	Doxorubicinol	Doxorubicinol aglycone
Experimental condition	(nmol/mg protein/4 h)
Ethanol → Dialysis	0.35	0.69
Paclitaxel → Dialysis	0.39	0.71
Docetaxel → Dialysis	0.32	0.60
Paclitaxel → Dialysis + Paclitaxel	0.59	1.1
Docetaxel → Dialysis + Docetaxel	0.62	1.2