Cytochrome P450 1B1 promotes cancer cell survival via specificity protein 1 (Sp1)-mediated suppression of death receptor 4

Journal of Toxicology and Environmental Health. Part a
Yeo-Jung KwonYoung-Jin Chun

Abstract

Cytochrome P450 1B1 (CYP1B1), a well-known oncogene, has garnered wide attention because of its tumor-specific expression pattern and actions as a carcinogenic factor. Although CYP1B1 might play a crucial role in carcinogenesis, the detailed molecular mechanisms underlying oncogenic involvement in cancer development remain unclear. The present study investigated the manner in which CYP1B1 promotes survival of various cancer cells. Treatment with 2,2',4,6'-tetramethoxystilbene (TMS), a specific CYP1B1 inhibitor, significantly inhibited cell viability in human breast cancer and leukemia cell lines, including MCF-7, MDA-MB-231, HL-60, and U937 cells. In order to characterize the cellular functions of CYP1B1 associated with cancer cell survival, the relationship between this oncogene and death receptor 4 (DR4) was determined. Following induction or inhibition of CYP1B1, mRNA and protein expression levels of DR4 were measured, and this oncogene was found to significantly repress DR4 mRNA and protein expression. Further, the suppression of DR4 by CYP1B1 was restored with 5-aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, indicating that DNA methylation may be involved in CYP1B1-mediated DR4 inhibition. Methylation-...Continue Reading

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Citations

Aug 3, 2019·Journal of Experimental & Clinical Cancer Research : CR·Francesca CirilloMarcello Maggiolini
Jan 24, 2021·Archives of Pharmacal Research·Yeo-Jung KwonYoung-Jin Chun
Dec 9, 2020·International Journal of Molecular Sciences·Tomas Koltai
Sep 1, 2021·Pharmacological Reports : PR·Beata Starek-ŚwiechowiczAndrzej Starek

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Methods Mentioned

BETA
transfection
transfections
scraping
electrophoresis
PCR
Protein Assay

Software Mentioned

Graph
Quantity One
- Pad Prism
GraphPad

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