5.19 The Case of Superoxide Dismutase Enzyme,
Interacting with Antitumor Drugs
Several investigations concerning with the definition of the activity of the copper–
zinc superoxide dismutase (Cu-Zn SOD) have been carried out, and the emerging
consensus is that the enzyme has usually, but not always, a lower activity in tumor
cells, with respect to normal cells [14]. Although the implication for carcinogenesis
and cancer chemotherapy of this activity loss is still unknown, this experimental
finding may be of importance in understanding the mode of action of antitumor
agents. There is a large class of cancer chemotherapeutic compounds that require as
a step in their reaction mechanism the production of superoxide O 2
− and/or other
oxygen-centered radicals, e.g., HO
Á , HO 2
Á , etc. These oxygen species are thought to
be responsible for the DNA damage that results in the cell’s destruction. Based on
the observation of a lowered SOD activity in cancer cells, one could anticipate that
an increased production of superoxide (e.g., induced by antitumor drugs) should
result in a preferential destruction of tumor cells. In addition, an antitumor drug
could further reduce the SOD activity by chelation with the enzyme active metal
site, e.g., Cu
2+ . Based on the works which considered the interaction between Cu
2+
and anthracyclines, the investigation was extended to the system Cu-Zn SOD—
anthracycline with the aim of assessing the accessibility of copper centers to the
drug molecules.
5.20 Discussion of the Case
Figure 5.15 reports two series of spectra concerning the interaction of Cu-Zn SOD
with doxorubicin, at different concentrations and for different r = drug/enzyme
molar ratios. The pattern is representative of the Cu-Zn SOD, g ‖ = 2.272 and
Table 5.3 ESR behavior of differently doped Ru-based glasses
Sample
no.
[RuO 2 ]
(mol%)
g l
g ?
Paramagnetic
species
10
5 [Ru
3+ ]
(at%)
10
5 Ru
3 þ
Â
Ã
Ru
4 þ
Â
Ã
72
0.10
1.91
2.40
Ru
3+
2.4
24
89
0.26
1.91
2.40
Ru
3+
5.2
20
75
0.43
1.91
2.40
Ru
3+
7.7
19
50
0.78
1.91
2.40
Ru
3+
8.9
13
39
1.19
1.91
2.40
Ru
3+
16.0
13
67
1.87
1.91
2.40
Ru
3+
31.0
16
46
2.40
1.91
2.40
Ru
3+
35.0
14
71
2.94
1.91
2.40
Ru
3+
48.0
16
60
3.50
1.91
2.40
Ru
3+
71.0
20
5.19 The Case of Superoxide Dismutase Enzyme, Interacting …
105
Interacting with Antitumor Drugs
Several investigations concerning with the definition of the activity of the copper–
zinc superoxide dismutase (Cu-Zn SOD) have been carried out, and the emerging
consensus is that the enzyme has usually, but not always, a lower activity in tumor
cells, with respect to normal cells [14]. Although the implication for carcinogenesis
and cancer chemotherapy of this activity loss is still unknown, this experimental
finding may be of importance in understanding the mode of action of antitumor
agents. There is a large class of cancer chemotherapeutic compounds that require as
a step in their reaction mechanism the production of superoxide O 2
− and/or other
oxygen-centered radicals, e.g., HO
Á , HO 2
Á , etc. These oxygen species are thought to
be responsible for the DNA damage that results in the cell’s destruction. Based on
the observation of a lowered SOD activity in cancer cells, one could anticipate that
an increased production of superoxide (e.g., induced by antitumor drugs) should
result in a preferential destruction of tumor cells. In addition, an antitumor drug
could further reduce the SOD activity by chelation with the enzyme active metal
site, e.g., Cu
2+ . Based on the works which considered the interaction between Cu
2+
and anthracyclines, the investigation was extended to the system Cu-Zn SOD—
anthracycline with the aim of assessing the accessibility of copper centers to the
drug molecules.
5.20 Discussion of the Case
Figure 5.15 reports two series of spectra concerning the interaction of Cu-Zn SOD
with doxorubicin, at different concentrations and for different r = drug/enzyme
molar ratios. The pattern is representative of the Cu-Zn SOD, g ‖ = 2.272 and
Table 5.3 ESR behavior of differently doped Ru-based glasses
Sample
no.
[RuO 2 ]
(mol%)
g l
g ?
Paramagnetic
species
10
5 [Ru
3+ ]
(at%)
10
5 Ru
3 þ
Â
Ã
Ru
4 þ
Â
Ã
72
0.10
1.91
2.40
Ru
3+
2.4
24
89
0.26
1.91
2.40
Ru
3+
5.2
20
75
0.43
1.91
2.40
Ru
3+
7.7
19
50
0.78
1.91
2.40
Ru
3+
8.9
13
39
1.19
1.91
2.40
Ru
3+
16.0
13
67
1.87
1.91
2.40
Ru
3+
31.0
16
46
2.40
1.91
2.40
Ru
3+
35.0
14
71
2.94
1.91
2.40
Ru
3+
48.0
16
60
3.50
1.91
2.40
Ru
3+
71.0
20
5.19 The Case of Superoxide Dismutase Enzyme, Interacting …
105