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Abstract
BackgroundThe cytochrome P450 CYP1A1 and CYP1B1 enzymes are involved in carcinogenesis via activation of pro-carcinogenic compounds to carcinogenic metabolites. CYP1A1 and CYP1B1 have shown elevated levels in human tumors as determined by qRT-PCR and immunohistochemical studies. However studies that have examined CYP1 expression by enzyme activity assays are limited. ResultsIn the current study the expression of CYP1A1 and CYP1B1 was investigated in a panel of human tumors of bladder and colorectal origin by qRT-PCR and enzyme activity assays. The results demonstrated that 35% (7/20) of bladder tumors and 35% (7/20) of colon tumors overexpressed active CYP1 enzymes. CYP1B1 mRNA was overexpressed in 65% and 60% of bladder and colon tumors respectively, whereas CYP1A1 was overexpressed in 65% and 80% of bladder and colon tumors. Mean mRNA levels of CYP1B1 and CYP1A1 along with mean CYP1 activity were higher in bladder and colon tumors compared to normal tissues (p<0.05). Statistical analysis revealed CYP1 expression levels to be independent of TNM status. Moreover, incubation of tumor microsomal protein in 4 bladder and 3 colon samples with a CYP1B1 specific antibody revealed a large reduction (72.5 ± 5.5 % for bladder and 71.8 ± 7.2% for colon) in catalytic activity, indicating that the activity was mainly attributed to CYP1B1 expression. ConclusionsThe study reveals active CYP1 overexpression in human tumors and uncovers the potential use of CYP1 enzymes and mainly CYP1B1 as targets for cancer therapy.
Highlights
Bladder and colon cancer are two of the most frequently encountered malignancies worldwide
Colon tumor tissues presented a higher frequency of CYP1A1 overexpression. 16 out 20 (80%) and 12 out of 20 (60%) samples showed significantly higher levels of CYP1A1 and CYP1B1 mRNA respectively in the tumor counterpart (Figure 2). 3 out of 20 samples revealed statistically lower CYP1A1 mRNA levels in tumors compared to normal pairs, while patient number 11 showed no significant change in CYP1A1 mRNA between tumor and normal tissue (Figure 2)
CYP1B1 mRNA levels were significantly lower in 6 out of 20 colon tumors compared to normal epithelia, whereas patients 13 and 4 presented non significant difference in CYP1B1 mRNA levels between normal and tumor tissues
Summary
Bladder and colon cancer are two of the most frequently encountered malignancies worldwide. CYP1A1 and CYP1B1 have shown elevated levels in human tumors as determined by qRT-PCR and immunohistochemical studies. Studies that have examined CYP1 expression by enzyme activity assays are limited. Results: In the current study the expression of CYP1A1 and CYP1B1 was investigated in a panel of human tumors of bladder and colorectal origin by qRT-PCR and enzyme activity assays. The results demonstrated that 35% (7/20) of bladder tumors and 35% (7/20) of colon tumors overexpressed active CYP1 enzymes. Mean mRNA levels of CYP1B1 and CYP1A1 along with mean CYP1 activity were higher in bladder and colon tumors compared to normal tissues (p
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