P450 1B1

Cytochrome P450 (P450) 1B1 is expressed in a number of human tissues in which cancers occur (e.g. prostate, ovary, uterus, mammary gland). P450 1B1 activates many environmental mutagens and also catalyzes the 4-hydroxylation of estrogens, considered to be an important step in hormonal carcinogenesis.

Background


An Overview of P450 1B1

Cytochrome P450 (CYP) 1B1 is one of the known members of cytochrome P450 supergene family and is the only member of CYP1B subfamily. It is overexpressed in many malignant tumors, especially in sex hormone dependent tumors. Studies of multiple series of primary and metastatic ovarian cancer tissues have revealed high frequency expression of CYP1Bl in primary and secondary tumors, making it an ideal target for tumor prevention and treatment. CYP1B1 is not only related to the etiology of sex hormone dependent tumors, but also may affect hormone metabolism and the formation of toxic metabolites. The human cytochrome P4501B1 gene is located on chromosome 2p22-21, and its DNA length is about 12 kb. It consists of three exons and two introns. It mR-NA size is 5.2 kb, encoding a protein containing 543 amino acids.

Inhibition of P450 1B1

Aromatic compounds containing vinyl and acetylene functional groups can selectively inhibit the metabolism of anticancer substances mediated by P450 1B1. CYPB is found in many tumor tissues. Rocha et al selected 12 compounds known to be metabolized by CYP, and investigated their inhibitory activity on CYPB1. The results showed that seven compounds have inhibitory effects on CYP 1B1, wherein flutamide, mitoxantrone, paclitaxel and docetaxel are competitive inhibitors of CYP 1B1.

P450 1B1 and diseases

It is a hot research topic to use fluorescent tumor markers or other chemicals to detect tumor tissues, and then use the imaging techniques or photodynamic therapy to diagnose and intervene tumor. It has been found that CYP 1B1, which is specifically and highly expressed in tumor tissues, can mediate fluorescent tumor markers and can be used in tumor diagnosis, photodynamic therapy and surgical localization. Several series of primary and metastatic ovarian cancer tissues have been studied and found that the overexpression of CYP 1B1 in primary and secondary tumors makes it an ideal target for tumor prevention and treatment.